Publications by authors named "Guiyuan Li"

360 Publications

Construction of a lncRNA-mRNA Co-Expression Network for Nasopharyngeal Carcinoma.

Front Oncol 2022 7;12:809760. Epub 2022 Jul 7.

Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, China.

Long non-coding RNAs (lncRNAs) widely regulate gene expression and play important roles in the pathogenesis of human diseases, including malignant tumors. However, the functions of most lncRNAs remain to be elucidated. In order to study and screen novel lncRNAs with important functions in the carcinogenesis of nasopharyngeal carcinoma (NPC), we constructed a lncRNA expression profile of 10 NPC tissues and 6 controls through a gene microarray. We identified 1,276 lncRNAs, of which most are unknown, with different expression levels in the healthy and NPC tissues. In order to shed light on the functions of these unknown lncRNAs, we first constructed a co-expression network of lncRNAs and mRNAs using bioinformatics and systematic biological approach. Moreover, mRNAs were clustered and enriched by their biological functions, and those lncRNAs have similar expression trends with mRNAs were defined as functional molecules with potential biological significance. The module may help identify key lncRNAs in the carcinogenesis of NPC and provide clues for in-depth study of their functions and associated signaling pathways. We suggest the newly identified lncRNAs may have clinic value as biomarkers and therapeutic targets for NPC diagnosis and treatment.
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http://dx.doi.org/10.3389/fonc.2022.809760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302896PMC
July 2022

NEDD4L inhibits cell viability, cell cycle progression, and glutamine metabolism in esophageal squamous cell carcinoma via ubiquitination of c-Myc.

Acta Biochim Biophys Sin (Shanghai) 2022 May 25. Epub 2022 May 25.

Department of Hematologic and Oncology, Xinjiang Clinical Research Center for Precision Medicine of Digestive System Tumor, the Center Hospital of Karamay City, Karamay 834000, China.

Esophageal squamous cell carcinoma (ESCC) is a common subtype of esophageal cancer with high incidence. Surgery remains the main strategy for treatment of ESCC at early stage. However, the treatment outcome is unsatisfactory. Therefore, finding new therapeutics is of great importance. In the present study, we measured the level of NEDD4L, an ubiquitin protein ligase, in clinical samples and investigated the effects of NEDD4L on cell viability, cell cycle progression, and glutamine metabolism in TE14 cells determined by CCK-8 assay, flow cytometry and biochemical analysis, respectively. The results show that NEDD4L is significantly decreased in ESCC specimens, and its decreased expression is associated with a poor clinical outcome. Overexpression of NEDD4L significantly inhibits cell viability, cell cycle progression, and glutamine metabolism in TE14 cells. Mechanistic study indicates that NEDD4L regulates tumor progression through ubiquitination of c-Myc and modulation of glutamine metabolism. NEDD4L inhibits cell viability, cell cycle progression, and glutamine metabolism in ESCC by ubiquitination of to decrease the expressions of GLS1 and SLC1A5. Our findings highlight the importance of NEDD4L/c-Myc signaling in ESCC.
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http://dx.doi.org/10.3724/abbs.2022048DOI Listing
May 2022

Metformin Inhibits Multiple Myeloma Serum-induced Endothelial Cell Thrombosis by Down-Regulating miR-532.

Ann Vasc Surg 2022 May 10. Epub 2022 May 10.

Department of Neurology, Karamay Central Hospital, Karamay, China. Electronic address:

Background: Thrombotic complications in multiple myeloma (MM) impairs the quality of life in patients. Metformin has a certain effect on anti-thrombosis, but its role and mechanism in MM-induced thrombosis are still uncovered. Therefore, this study evaluated the effect of metformin on MM-induced thrombosis.

Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to normal serum (15%), MM serum (15%), metformin (0.01 mmol/L), or MM serum, and metformin simultaneously. The expression of tissue factor (TF) in HUVECs was detected by flow cytometry and quantitative real-time polymerase chain reaction PCR (qRT-PCR). QRT-PCR was also used to determine the expressions of endothelial protein C receptor (EPCR) and miR-532. The generation of thrombin and activated protein C was measured by thrombin generation and protein C activation assays. EPCR, extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathway related protein expressions were detected by western blot.

Results: MM serum increased the expressions of TF and miR-532, induced thrombin generation, inhibited EPCR and protein C activation in HUVECs. And metformin could reverse the effects of MM serum on the expressions of TF, EPCR and miR-532, thrombin generation, protein C activation in HUVECs. However, miR-532 mimic reversed the effects of metformin and promoted the levels of thrombosis-related indicators in HUVECs. Moreover, metformin activated the ERK 1/2, p38 MAPK, and NF-κB pathways but miR-532 mimic suppressed the pathway activation.

Conclusions: Metformin played an inhibitory effect on MM serum-induced HUVEC thrombosis, suggesting that metformin could serve as a novel antithrombotic approach for MM patients.
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http://dx.doi.org/10.1016/j.avsg.2022.04.035DOI Listing
May 2022

B cells and tumor immune escape.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2022 Mar;47(3):358-363

Cancer Research Institute, Central South University, Changsha 410078.

B lymphocyte is an important component of the human immune system and it has a role in the process of the body's specific immunity. In recent years, the research on B cells and tumor immune escape has rapidly progressed. Studies have shown that different types of B cells play different roles in tumor microenvironment through a variety of mechanisms. B cells in the tertiary lymphatic structure promote anti-tumor immunity, while regulatory B cells promote tumor immune escape. Antibody drugs targeting B cells are a promising direction for tumor immunotherapy.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2022.210275DOI Listing
March 2022

Extrachromosomal Circular DNA: A New Target in Cancer.

Front Oncol 2022 14;12:814504. Epub 2022 Apr 14.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Genomic instability and amplification are intrinsically important traits determining the development and heterogeneity of tumors. The role of extrachromosomal circular DNA (eccDNA) in tumors has recently been highlighted. EccDNAs are unique genetic materials located off the chromosomal DNA. They have been detected in a variety of tumors. This review analyzes the mechanisms involved in the formation of eccDNAs and their genetic characteristics. In addition, the high-copy number and transcriptional levels of oncogenes located in eccDNA molecules contribute to the acceleration of tumor evolution and drug resistance and drive the development of genetic heterogeneity. Understanding the specific genomic forms of eccDNAs and characterizing their potential functions will provide new strategies for tumor therapy. Further research may yield new targets and molecular markers for the early diagnosis and treatment of human cancer.
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http://dx.doi.org/10.3389/fonc.2022.814504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046939PMC
April 2022

Circular RNA circCCNB1 inhibits the migration and invasion of nasopharyngeal carcinoma through binding and stabilizing TJP1 mRNA.

Sci China Life Sci 2022 Apr 21. Epub 2022 Apr 21.

Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410083, China.

Nasopharyngeal carcinoma (NPC) is a malignant tumor that usually occurs in people from Southeast Asia and Southern China. NPC is prone to migration and invasion, leading to poor prognosis. A large number of circular RNAs (circRNAs) exacerbate the process of metastasis in NPC; however, their underlying mechanisms remain unclear. We found that the circular RNA circCCNB1, encoded by the oncogene CCNB1, was downregulated in NPC biopsies and cell lines. In vitro assays show that circCCNB1 inhibits NPC cell migration and invasion. Moreover, circCCNB1 induces a protein, nuclear factor 90 (NF90), to bind and prolong the half-life of tight junction protein 1 (TJP1) mRNA. Upregulation of TJP1 enhances tight junctions between cancer cells and inhibits NPC cell migration and invasion. This study reveals a novel biological function of circCCNB1 in the migration and invasion of NPC by enhancing the tight junctions of cancer cells by binding to NF90 proteins and TJP1 mRNA, and may provide a potential therapeutic target for NPC.
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http://dx.doi.org/10.1007/s11427-021-2089-8DOI Listing
April 2022

The emerging roles of the interaction between m6A modification and c-Myc in driving tumorigenesis and development.

J Cell Physiol 2022 07 6;237(7):2758-2769. Epub 2022 Apr 6.

NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

N6-methyladenosine (m6A) is an extremely common and conservative posttranscriptional modification, that can specifically target and regulate the expression or stability of a series of tumor-related genes, thus playing critical roles in the occurrence and development of tumors. c-Myc is an important tumorigenic transcription factor that promotes tumorigenesis and development by mainly regulating the expression of downstream target genes. Increasing evidence shows that m6A modification, as well as abnormal expression and regulation of c-Myc, is critical molecular mechanisms driving tumorigenesis and development. Although more evidence has been uncovered about the individual roles of m6A modification or c-Myc in tumors, the interaction between m6A modification and c-Myc in tumorigenesis and development has not been systematically summarized. Therefore, this review is focused on the mutual regulation between m6A modification and c-Myc expression and stability as well as its roles in tumorigenesis and development. We also summarized the potential value of the interaction between m6A modification and m6A expression and stability in tumor diagnosis and treatment, which provides a specific reference for revealing the mechanism of tumor occurrence and development as well as clinical diagnosis and treatment.
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http://dx.doi.org/10.1002/jcp.30733DOI Listing
July 2022

BRD7 Stabilizes P53 via Dephosphorylation of MDM2 to Inhibit Tumor Growth in Breast Cancer Harboring Wild-type P53.

J Cancer 2022 28;13(5):1436-1448. Epub 2022 Feb 28.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.

Bromodomain-containing protein 7 (BRD7) was found to be down-expressed in nasopharyngeal carcinoma as well as breast cancer and to function as a potential tumor suppressor. BRD7 interacts with p53 and is required for p53-dependent oncogene-induced senescence. However, the mechanism how BRD7 functions as tumor suppressor roles in breast cancer remains unclear. MTT, colony formation assay, cell cycle, cell apoptosis, and tumorigenicity assays were performed to evaluate the biological functions of BRD7 in breast cancer cells . Real-time PCR, western blot, luciferase reporter gene assays, and co-immunoprecipitation were used to examine the gene expression, transcription activation and protein-protein interaction. We reported that BRD7 effectively suppressed cell proliferation and tumor growth and . In addition, BRD7 increased p53 protein stability through ubiquitin-dependent proteasome pathway and regulated the expression of p53 downstream target genes by activating its transcriptional activity in breast cancers harboring wild-type p53. Mechanistically, BRD7 decreased phosphorylation and activation of MDM2 via inactivating its upstream kinase AKT depending on the bromodomain of BRD7, therefore BRD7 significantly reduced the amounts of phosphorylated MDM2 binding with p53 eventually decreasing ubiquitination level of p53. Furthermore, silencing the expression of p53 at least partly reversed the inhibition effect of BRD7 on cell proliferation and tumor growth and . Our studies identify that BRD7 stabilizes p53 by inhibiting the phosphorylation of MDM2 via AKT pathway dependent on its bromodomain to function as a tumor suppressor in breast cancer harboring wild-type p53.
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http://dx.doi.org/10.7150/jca.67447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965117PMC
February 2022

Splicing factor derived circular RNA circCAMSAP1 accelerates nasopharyngeal carcinoma tumorigenesis via a SERPINH1/c-Myc positive feedback loop.

Mol Cancer 2022 02 28;21(1):62. Epub 2022 Feb 28.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Background: Circular RNAs play an important role in tumor genesis and progression, but they have not been sufficiently studied in patients with nasopharyngeal carcinoma (NPC).

Methods: The circular RNA, circCAMSAP1, was screened in NPC cells by RNA sequencing analysis. The expression of circCAMSAP1 in NPC tissues was examined by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization. Wound-healing, transwell, MTT and flow cytometry assays, and nude mouse tumor models were used to explore the effect of circCAMSAP1 on proliferation and metastasis of NPC in vitro or in vivo. The downstream proteins regulated by circCAMSAP1 were screened using mass spectrometry. The interaction between circCAMSAP1 and the SERPINH1 mRNA was identified using the circular RNA immunoprecipitation method and the luciferase reporter assay. The interaction between SERPINH1 and transcription factor c-Myc was verified through Co-immunoprecipitation (Co-IP) and immunofluorescence. The effect of c-Myc on the generation of circCAMSAP1 was examined through RT-qPCR and chromatin immunoprecipitation. Finally, the splicing factors that promote the production of circCAMSAP1 were explored by RT-qPCR and RNA immunoprecipitation (RIP).

Results: We found that circCAMSAP1 was highly expressed in NPC tissues and promoted NPC proliferation and metastasis. Additionally, circCAMSAP1 promoted SERPINH1 expression through improved SERPINH1 mRNA stability by binding to the 3'-untranslated region (3'UTR) of SERPINH1. Highly expressed SERPINH1 reduced the ubiquitination-degradation rate of c-Myc, causing increased tumorigenesis. Meanwhile, c-Myc, cooperating with splicing factor 10 (SRSF10), could also promote CAMSAP1 pre-mRNA transcription and back-splicing, forming a positive feedback of circCAMSAP1 production, resulting in the proliferation and metastasis of NPC.

Conclusions: Our findings revealed that circCAMSAP1 promotes NPC proliferation and metastasis by binding to the 3'UTR of SERPINH1, suggesting that the positive feedback of circCAMSAP1-SERPINH1-c-Myc may serve as a prognostic biomarker or therapeutic target in patients with NPC.
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http://dx.doi.org/10.1186/s12943-022-01502-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883650PMC
February 2022

The Role of the SOX9/lncRNA ANXA2P2/miR-361-3p/SOX9 Regulatory Loop in Cervical Cancer Cell Growth and Resistance to Cisplatin.

Front Oncol 2021 10;11:784525. Epub 2022 Jan 10.

Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China.

Cervical cancer is a highly prevalent female malignancy. Presently, cisplatin (DDP) is a first-line agent for cervical cancer chemotherapy. However, its curative effect is limited because of chemo-resistance. It has been previously reported that SOX9 targeted and activated oncogenic genes, enhancing cervical cancer cell resistance to DDP. The effects of the SOX9/lncRNA ANXA2P2/miR-361-3p/SOX9 regulatory loop on cervical cancer cell growth and resistance to DDP have been demonstrated. miR-361-3p expression was decreased in DDP-resistant cervical cancer cells and tissues. Moreover, miR-361-3p overexpression inhibited the growth of resistant cervical cancer cells and the resistance to DDP, whereas miR-361-3p inhibition exerted opposite effects. miR-361-3p inhibited SOX9 expression through binding; the effects of miR-361-3p inhibition were partially reversed by SOX9 knockdown. LncRNA ANXA2P2 expression was elevated in DDP-resistant cervical cancer cells and tissues. LncRNA ANXA2P2 inhibited miR-361-3p expression by binding, thereby upregulating SOX9. LncRNA ANXA2P2 knockdown inhibited DDP-resistant cervical cancer cell growth and resistance to DDP, whereas the effects of lncRNA ANXA2P2 knockdown were partially reversed by miR-361-3p inhibition. SOX9 expression was elevated in DDP-resistant cervical cancer cells and tissues, and SOX9 activated lncRNA ANXA2P2 transcription by binding. Collectively, SOX9, lncRNA ANXA2P2, and miR-361-3p form a regulatory loop, modulating DDP-resistant cervical cancer cell growth and response to DDP treatment.
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http://dx.doi.org/10.3389/fonc.2021.784525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784813PMC
January 2022

Potential biomarkers of acute myocardial infarction based on co-expression network analysis.

Exp Ther Med 2022 Feb 21;23(2):162. Epub 2021 Dec 21.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.

Acute myocardial infarction (AMI) is a common cause of death in numerous countries. Understanding the molecular mechanisms of the disease and analyzing potential biomarkers of AMI is crucial. However, specific diagnostic biomarkers have thus far not been fully established and candidate regulatory targets for AMI remain to be determined. In the present study, the AMI gene chip dataset GSE48060 comprising blood samples from control subjects with normal cardiac function (n=21) and patients with AMI (n=26) was downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) between the AMI and control groups were identified with the online tool GEO2R. The co-expression network of DEGs was analyzed by calculating the Pearson correlation coefficient of all gene pairs, mutual rank screening and cutoff threshold screening. Subsequently, the Gene Ontology (GO) database was used to analyze the genes' functions and pathway enrichment of genes in the most important modules was performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) Disease and BioCyc were used to analyze the hub genes in the module to determine important sub-pathways. In addition, the expression of hub genes was confirmed by reverse transcription-quantitative PCR in AMI and control specimens. In the present study, 52 DEGs, including 26 upregulated and 26 downregulated genes, were identified. As key hub genes, three upregulated genes (AKR1C3, RPS24 and P2RY12) and three downregulated genes (ACSL1, B3GNT5 and MGAM) were identified from the co-expression network. Furthermore, GO enrichment analysis of all AMI co-expression network genes revealed functional enrichment mainly in 'RAGE receptor binding' and 'negative regulation of T cell cytokine production'. In addition, KEGG Disease and BioCyc analysis indicated functional enrichment of the genes RPS24 and P2RY12 in 'cardiovascular diseases', of AKR1C3 in 'cardenolide biosynthesis', of MGAM in 'glycogenolysis', of B3GNT5 in 'glycosphingolipid biosynthesis' and of ACSL1 in 'icosapentaenoate biosynthesis II'. In conclusion, the hub genes AKR1C3, RPS24, P2RY12, ACSL1, B3GNT5 and MGAM are potential markers of AMI, and have potential application value in the diagnosis of AMI.
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http://dx.doi.org/10.3892/etm.2021.11085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753964PMC
February 2022

Recent advances of fluorescent biosensors based on cyclic signal amplification technology in biomedical detection.

J Nanobiotechnology 2021 Dec 4;19(1):403. Epub 2021 Dec 4.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

The cyclic signal amplification technology has been widely applied for the ultrasensitive detection of many important biomolecules, such as nucleic acids, proteins, enzymes, adenosine triphosphate (ATP), metal ions, exosome, etc. Due to their low content in the complex biological samples, traditional detection methods are insufficient to satisfy the requirements for monitoring those biomolecules. Therefore, effective and sensitive biosensors based on cyclic signal amplification technology are of great significance for the quick and simple diagnosis and treatment of diseases. Fluorescent biosensor based on cyclic signal amplification technology has become a research hotspot due to its simple operation, low cost, short time, high sensitivity and high specificity. This paper introduces several cyclic amplification methods, such as rolling circle amplification (RCA), strand displacement reactions (SDR) and enzyme-assisted amplification (EAA), and summarizes the research progress of using this technology in the detection of different biomolecules in recent years, in order to provide help for the research of more efficient and sensitive detection methods.
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http://dx.doi.org/10.1186/s12951-021-01149-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645109PMC
December 2021

A fluorescence strategy for circRNA quantification in tumor cells based on T7 nuclease-assisted cycling enzymatic amplification.

Anal Chim Acta 2022 Jan 26;1189:339210. Epub 2021 Oct 26.

NHC Key Laboratory of Carcinogenesis and Human Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address:

Circular Ribonucleic Acid (CircRNA) plays regulatory roles in many biological processes, such as tumors and metabolic diseases. Due to the fact that circRNA is more stable and conservative than linear RNA, circRNA has become a potential biomarker in early clinical diagnosis and biomedical research. Therefore, the quantification of circRNA expression level is of importance for understanding their functions and their applications for disease diagnosis and treatment. Nevertheless, due to the low abundance of circRNA, it is still a challenge for the analysis of circRNA in cells. Herein, we proposed a sensitive detection method for circRNA based on the T7 exonuclease-assisted cycling enzymatic amplification. The fluorescent sensor was constructed by a hairpin molecular beacon and T7 exonuclease. With the cycling enzymatic amplification process, this sensor achieved the limit of detection of 1 pM with a good linear correlation in the range of 0-100 pM (R = 0.9891) using circBART2.2 as a model. Furthermore, we applied the proposed method in the determination of circBART2.2 in cell lysates. The results demonstrated that this method has promising applications in early diagnosis of Epstein-Barr virus (EBV) infection-related diseases using circRNA as the biomarker.
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http://dx.doi.org/10.1016/j.aca.2021.339210DOI Listing
January 2022

The role of alternative splicing in human cancer progression.

Am J Cancer Res 2021 15;11(10):4642-4667. Epub 2021 Oct 15.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University Changsha 410013, Hunan, China.

In eukaryotes, alternative splicing refers to a process via which a single precursor RNA (pre-RNA) is transcribed into different mature RNAs. Thus, alternative splicing enables the translation of a limited number of coding genes into a large number of proteins with different functions. Although, alternative splicing is common in normal cells, it also plays an important role in cancer development. Alteration in splicing mechanisms and even the participation of non-coding RNAs may cause changes in the splicing patterns of cancer-related genes. This article reviews the latest research on alternative splicing in cancer, with a view to presenting new strategies and guiding future studies related to pathological mechanisms associated with cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569372PMC
October 2021

Long non-coding RNAs are involved in alternative splicing and promote cancer progression.

Br J Cancer 2022 05 8;126(8):1113-1124. Epub 2021 Nov 8.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Alternative splicing (AS) is a key process in which precursor RNAs produce different mature RNAs, and the disorder of AS is a key factor in promoting cancer development. Compared with coding RNA, studies on the functions of long non-coding RNAs (lncRNAs) are far from enough. In fact, lncRNA is an important participant and regulator in the process of AS. On the one hand, lncRNAs regulate cancer progression as AS products of precursor messenger RNA (mRNA), but on the other hand, precursor lncRNA generates cancer-related abnormal splicing variants through AS. In addition, lncRNAs directly or indirectly regulate the AS events of downstream target genes, thus affecting the occurrence and development of cancer. Here, we reviewed how lncRNAs regulate AS and influence oncogenesis in different ways.
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http://dx.doi.org/10.1038/s41416-021-01600-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023592PMC
May 2022

Correction to: TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development.

Cell Mol Life Sci 2021 Dec 2;78(23):7915. Epub 2021 Nov 2.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.

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http://dx.doi.org/10.1007/s00018-021-03982-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172676PMC
December 2021

BPIFB1 inhibits vasculogenic mimicry via downregulation of GLUT1-mediated H3K27 acetylation in nasopharyngeal carcinoma.

Oncogene 2022 01 1;41(2):233-245. Epub 2021 Nov 1.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Nasopharyngeal carcinoma (NPC) demonstrates significant regional differences and a high incidence in Southeast Asia and Southern China. Bactericidal/permeability-increasing-fold- containing family B member 1 (BPIFB1) is a relatively specific and highly expressed protein in the nasopharyngeal epithelium. BPIFB1 expression is substantially downregulated in NPC and is significantly associated with poor prognosis in patients with NPC. However, the specific molecular mechanism by which BPIFB1 regulates NPC is not well understood. In this study, we found that BPIFB1 inhibits vasculogenic mimicry by regulating the metabolic reprogramming of NPC. BPIFB1 decreases GLUT1 transcription by downregulating the JNK/AP1 signaling pathway. Altered glycolysis reduces the acetylation level of histone and decreases the expression of vasculogenic mimicry-related genes, VEGFA, VE-cadherin, and MMP2, ultimately leading to the inhibition of vasculogenic mimicry. To our knowledge, this is the first report on the role and specific mechanism of BPIFB1 as a tumor suppressor gene involved in regulating glycolysis and vasculogenic mimicry in NPC. Overall, these results provide a new therapeutic target for NPC diagnosis and treatment.
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http://dx.doi.org/10.1038/s41388-021-02079-8DOI Listing
January 2022

Correction to: Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ.

J Exp Clin Cancer Res 2021 Sep 22;40(1):298. Epub 2021 Sep 22.

Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Tongzipo Road, Changsha, 410013, Hunan, China.

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http://dx.doi.org/10.1186/s13046-021-02100-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456600PMC
September 2021

Correction to: Pyroptosis: a new paradigm of cell death for fighting against cancer.

J Exp Clin Cancer Res 2021 Sep 22;40(1):296. Epub 2021 Sep 22.

Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Tongzipo Road, Changsha, 410013, Hunan, China.

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http://dx.doi.org/10.1186/s13046-021-02101-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456663PMC
September 2021

Circular RNA circRNF13 inhibits proliferation and metastasis of nasopharyngeal carcinoma via SUMO2.

Mol Cancer 2021 08 31;20(1):112. Epub 2021 Aug 31.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China.

Background: Circular RNAs (circRNAs) are widely expressed in human cells and are closely associated with cancer development. However, they have rarely been investigated in the context of nasopharyngeal carcinoma (NPC).

Methods: We screened a new circRNA, circRNF13, in NPC cells using next-generation sequencing of mRNA. Reverse transcription polymerase chain reaction and RNA fluorescence in situ hybridization were used to detect circRNF13 expression in 12 non-tumor nasopharyngeal epithelial (NPE) tissues and 36 NPC samples. Cell proliferation was detected using MTT and flow cytometry assays, and colony formation capability was detected using colony formation assays. Cell migration and invasion were analyzed using wound-healing and Transwell assays, respectively. Cell glycolysis was analyzed using the Seahorse glycolytic stress test. Glucose transporter type 1 (GLUT1) ubiquitination and SUMOylation modifications were analyzed using co-immunoprecipitation and western blotting. CircRNF13 and Small Ubiquitin-like Modifier 2 (SUMO2) interactions were analyzed using RNA pull-down and luciferase reporter assays. Finally, to test whether circRNF13 inhibited NPC proliferation and metastasis in vivo, we used a xenograft nude mouse model generated by means of subcutaneous or tail vein injection.

Results: We found that circRNF13 was stably expressed at low levels in NPC clinical tissues and NPC cells. In vitro and in vivo experiments showed that circRNF13 inhibited NPC proliferation and metastasis. Moreover, circRNF13 activated the SUMO2 protein by binding to the 3'- Untranslated Region (3'-UTR) of the SUMO2 gene and prolonging the half-life of SUMO2 mRNA. Upregulation of SUMO2 promotes GLUT1 degradation through SUMOylation and ubiquitination of GLUT1, which regulates the AMPK-mTOR pathway by inhibiting glycolysis, ultimately resulting in the proliferation and metastasis of NPC.

Conclusions: Our results revealed that a novel circRNF13 plays an important role in the development of NPC through the circRNF13-SUMO2-GLUT1 axis. This study implies that circRNF13 mediates glycolysis in NPC by binding to SUMO2 and provides an important theoretical basis for further elucidating the pathogenesis of NPC and targeted therapy.
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http://dx.doi.org/10.1186/s12943-021-01409-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406723PMC
August 2021

Epstein-Barr Virus-Encoded Circular RNA CircBART2.2 Promotes Immune Escape of Nasopharyngeal Carcinoma by Regulating PD-L1.

Cancer Res 2021 10 28;81(19):5074-5088. Epub 2021 Jul 28.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Epstein-Barr virus (EBV) infection is an established cause of nasopharyngeal carcinoma (NPC) and is involved in a variety of malignant phenotypes, including tumor immune escape. EBV can encode a variety of circular RNAs (circRNA), however, little is known regarding the biological functions of these circRNAs in NPC. In this study, EBV-encoded was found to be highly expressed in NPC where it upregulated PD-L1 expression and inhibited T-cell function and . promoted transcription of PD-L1 by binding the helicase domain of RIG-I and activating transcription factors IRF3 and NF-κB, resulting in tumor immune escape. These results elucidate the biological function of , explain a novel mechanism of immune escape caused by EBV infection, and provide a new immunotherapy target for treating NPC. SIGNIFICANCE: This work demonstrates that binding to RIG-I is essential for the regulation of PD-L1 and subsequent immune escape in nasopharyngeal carcinoma.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-4321DOI Listing
October 2021

Correction to: Pyroptosis: a new paradigm of cell death for fighting against cancer.

J Exp Clin Cancer Res 2021 Jul 1;40(1):219. Epub 2021 Jul 1.

NHC Key Laboratory of Carcinogenesis, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Tongzipo Road, Changsha, 410013, Hunan, China.

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http://dx.doi.org/10.1186/s13046-021-02020-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247097PMC
July 2021

Potassium Channel Protein KCNK6 Promotes Breast Cancer Cell Proliferation, Invasion, and Migration.

Front Cell Dev Biol 2021 14;9:616784. Epub 2021 Jun 14.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Breast cancer is the most common malignant tumor in women, and its incidence is increasing each year. To effectively treat breast cancer, it is important to identify genes involved in its occurrence and development and to exploit them as potential drug therapy targets. Here, we found that potassium channel subfamily K member 6 (KCNK6) is significantly overexpressed in breast cancer, however, its function in tumors has not been reported. We further verified that KCNK6 expression is upregulated in breast cancer biopsies. Moreover, overexpressed KCNK6 was found to enhance the proliferation, invasion, and migration ability of breast cancer cells. These effects may occur by weakening cell adhesion and reducing cell hardness, thus affecting the malignant phenotype of breast cancer cells. Our study confirmed, for the first time, that increased KCNK6 expression in breast cancer cells may promote their proliferation, invasion, and migration. Moreover, considering that ion channels serve as therapeutic targets for many small molecular drugs in clinical treatment, targeting KCNK6 may represent a novel strategy for breast cancer therapies. Hence, the results of this study provide a theoretical basis for KCNK6 to become a potential molecular target for breast cancer treatment in the future.
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http://dx.doi.org/10.3389/fcell.2021.616784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237943PMC
June 2021

Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc.

Signal Transduct Target Ther 2021 06 25;6(1):240. Epub 2021 Jun 25.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Actin filament associated protein 1 antisense RNA 1 (named AFAP1-AS1) is a long non-coding RNA and overexpressed in many cancers. This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer. The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization. The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells. To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer, we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses. AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients' poor prognosis. In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis. AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1 (named SNIP1), which inhibited ubiquitination and degradation of c-Myc protein. Upregulation of c-Myc molecule in turn promoted the expression of ZEB1, ZEB2, and SNAIL gene, which ultimately enhanced epithelial to mesenchymal transition (EMT) and lung cancer metastasis. Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer's migration and invasion may provide novel therapeutic targets for lung cancer patients' early diagnosis and therapy.
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http://dx.doi.org/10.1038/s41392-021-00562-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225811PMC
June 2021

Genome instability and lymphoma.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 May;46(5):552-557

Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha 410078, China.

Lymphoma is one of the most common malignant tumor of the hematologic system. The genome instability is not only an important molecular basis for the development of lymphoma, but also has important value in the diagnosis and prognosis of lymphoma. There are 2 types of genome instability: Microsatellite instability (MSI/MIN) at gene level and chromosomal instability at chromosome level. Through the study on genes associated with lymphoma, the unstable genes associated with lymphoma could be found, meanwhile the mechanism of its occurrence and development of lymphoma could be explored, and the important basis of molecular biology could also be provided in the field of current hot lymphoma precision medical research.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.190427DOI Listing
May 2021

BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer.

Front Cell Dev Biol 2021 24;9:659392. Epub 2021 May 24.

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

BRD7 functions as a crucial tumor suppressor in numerous malignancies. However, the effects of BRD7 on colorectal cancer (CRC) progression are still unknown. Here, based on the BRD7 knockout (BRD7) and BRD7 (BRD7) mouse models constructed in our previous work, we established an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse model. BRD7 mice were found to be highly susceptible to AOM/DSS-induced colitis-associated CRC, and BRD7 significantly promoted cell proliferation and cell cycle G1/S transition but showed no significant effect on cell apoptosis. Furthermore, BRD7 interacted with c-Myc and stabilized c-Myc by inhibiting its ubiquitin-proteasome-dependent degradation. Moreover, restoring the expression of c-Myc in BRD7-silenced CRC cells restored cell proliferation, cell cycle progression, and tumor growth and . In addition, BRD7 and c-Myc were both significantly upregulated in CRC patients, and high expression of these proteins was associated with clinical stage and poor prognosis in CRC patients. Collectively, BRD7 functions as an oncogene and promotes CRC progression by regulating the ubiquitin-proteasome-dependent stabilization of c-Myc protein. Targeting the BRD7/c-Myc axis could be a potential therapeutic strategy for CRC.
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http://dx.doi.org/10.3389/fcell.2021.659392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181413PMC
May 2021

Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ.

J Exp Clin Cancer Res 2021 Jun 9;40(1):190. Epub 2021 Jun 9.

Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Tongzipo Road, Changsha, 410013, Hunan, China.

Background: Pyroptosis is a lytic cell death form executed by gasdermins family proteins. Induction of tumor pyroptosis promotes anti-tumor immunity and is a potential cancer treatment strategy. Triptolide (TPL) is a natural product isolated from the traditional Chinese herb which possesses potent anti-tumor activity in human cancers. However, its role in pyroptosis remains to be elucidated.

Methods: Cell survival was measured by colony formation assay. Cell apoptosis was determined by Annexin V assay. Pyroptosis was evaluated by morphological features and release of interleukin 1β and lactate dehydrogenase A (LDHA). Immunofluorescence staining was employed to measure subcellular localization of proteins. Tumorigenicity was assessed by a xenograft tumor model. Expression levels of mRNAs or proteins were determined by qPCR or western blot assay, respectively.

Results: Triptolide eliminates head and neck cancer cells through inducing gasdermin E (GSDME) mediated pyroptosis. Silencing GSDME attenuates the cytotoxicity of TPL against cancer cells. TPL treatment suppresses expression of c-myc and mitochondrial hexokinase II (HK-II) in cancer cells, leading to activation of the BAD/BAX-caspase 3 cascade and cleavage of GSDME by active caspase 3. Silencing HK-II sensitizes cancer cells to TPL induced pyroptosis, whereas enforced expression of HK-II prevents TPL induced pyroptosis. Mechanistically, HK-II prevents mitochondrial translocation of BAD, BAX proteins and activation of caspase 3, thus attenuating cleavage of GSDME and pyroptosis upon TPL treatment. Furthermore, TPL treatment suppresses NRF2/SLC7A11 (also known as xCT) axis and induces reactive oxygen species (ROS) accumulation, regardless of the status of GSDME. Combination of TPL with erastin, an inhibitor of SLC7A11, exerts robust synergistic effect in suppression of tumor survival in vitro and in a nude mice model.

Conclusions: This study not only provides a new paradigm of TPL in cancer therapy, but also highlights a crucial role of mitochondrial HK-II in linking glucose metabolism with pyroptosis.
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http://dx.doi.org/10.1186/s13046-021-01995-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188724PMC
June 2021

Lung microbiome alterations in NSCLC patients.

Sci Rep 2021 06 3;11(1):11736. Epub 2021 Jun 3.

Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Lung is colonized by a diverse array of microbes and the lung microbiota is profoundly involved in the development of respiratory diseases. There is little knowledge about the role of lung microbiota dysbiosis in lung cancer. In this study, we performed metagenomic sequencing on bronchoalveolar lavage (BAL) from two different sampling methods in non-small cell lung cancer (NSCLC) patients and non-cancer controls. We found the obvious variation between bronchoscopy samples and lobectomy samples. Oral taxa can be found in both bronchoscopy and lobectomy samples and higher abundance of oral taxa can be found in bronchoscopy samples. Although the NSCLC patients had similar microbial communities with non-cancer controls, rare species such as Lactobacillus rossiae, Bacteroides pyogenes, Paenibacillus odorifer, Pseudomonas entomophila, Magnetospirillum gryphiswaldense, fungus Chaetomium globosum et al. showed obvious difference between NSCLC patients and non-cancer controls. Age-, gender-, and smoking-specific species and EGFR expression-related species in NSCLC patients were detected. There results implicated that different lung segments have differential lung microbiome composition. The oral taxa are found in the lobectomy samples suggesting that oral microbiota are the true members of lung microbiota, rather than contamination during bronchoscopy. Lung cancer does not obviously alter the global microbial composition, while rare species are altered more than common species. Certain microbes may be associated with lung cancer progression.
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http://dx.doi.org/10.1038/s41598-021-91195-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175694PMC
June 2021

AFAP1-AS1: a rising star among oncogenic long non-coding RNAs.

Sci China Life Sci 2021 Oct 13;64(10):1602-1611. Epub 2021 May 13.

NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education of China, Cancer Research Institute, Central South University, Changsha, 410078, China.

Long non-coding RNAs (lncRNAs) have become a hotspot in biomedical research. This interest reflects their extensive involvement in the regulation of the expression of other genes, and their influence on the occurrence and development of a variety of human diseases. Actin filament associated protein 1-Antisense RNA 1(AFAP1-AS1) is a recently discovered oncogenic lncRNA. It is highly expressed in a variety of solid tumors, and regulates the expression of downstream genes and signaling pathways through adsorption and competing microRNAs, or by the direct binding to other proteins. Ultimately, AFAP1-AS1 promotes proliferation, chemotherapy resistance, and resistance to apoptosis, maintains stemness, and enhances invasion and migration of tumor cells. This paper summarizes the research concerning AFAP1-AS1 in malignant tumors, including the clinical application prospects of AFAP1-AS1 as a potential molecular marker and therapeutic target of malignant tumors. We also discuss the limitations in the knowledge of AFAP1-AS1 and directions of further research. AFAP1-AS1 is expected to provide an example for studies of other lncRNA molecules.
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http://dx.doi.org/10.1007/s11427-020-1874-6DOI Listing
October 2021

Research Progress of circRNAs in Head and Neck Cancers.

Front Oncol 2021 29;11:616202. Epub 2021 Apr 29.

Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Because of their characteristics of a closed loop structure, disease- and tissue-specificity, and high conservation and stability, circRNAs have the potential to be biomarkers for disease diagnosis. Head and neck cancers are one of the most common malignant tumors with high incidence rates globally. Affected patients are often diagnosed at the advanced stage with poor prognosis, owing to the concealment of anatomic sites. The characteristics, functions, and specific mechanisms of circRNAs in head and neck cancers are increasingly being discovered, and they have important clinical significance for the early diagnosis, treatment, and prognosis evaluation of patients with cancer. In this study, the generation, characteristics, and functions of circRNAs, along with their regulatory mechanisms in head and neck cancers have been summarized. We report that circRNAs interact with molecules such as transcription and growth factors to influence specific pathways involved in tumorigenesis. We conclude that circRNAs have an important role to play in the proliferation, invasion, metastasis, energy and substance metabolism, and treatment resistance in cancers.
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http://dx.doi.org/10.3389/fonc.2021.616202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117014PMC
April 2021
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