Publications by authors named "Xiaodan Meng"

23 Publications

  • Page 1 of 1

Evaluation of EpCAM-specific exosomal lncRNAs as potential diagnostic biomarkers for lung cancer using droplet digital PCR.

J Mol Med (Berl) 2022 Jan 14;100(1):87-100. Epub 2021 Oct 14.

Department of Thoracic Surgery, The Affiliated Hospital of Medical School of Ningbo University, 247 Renmin Road, Ningbo, 315020, Zhejiang, China.

Accumulating evidence demonstrated that long non-coding RNAs (lncRNAs) derived from exosomes had the potential to be diagnostic markers for lung cancer. However, the diagnostic value of lncRNAs from epithelial cell adhesion molecule (EpCAM)-positive exosomes remains unclear. In the study, serum EpCAM-positive exosomes were isolated with magnetic beads, and their role in lung cancer was investigated in vitro and in vivo. The copy numbers of lncRNAs RP11-77G23.5 and PHEX-AS1 in EpCAM-specific exosomes were quantified by droplet digital PCR (ddPCR). The diagnostic value of RP11-77G23.5 and PHEX-AS1 was tested in the training cohort and verified in the validation cohort. We found that EpCAM-specific exosomes could promote lung cancer development in vitro and in vivo. RP11-77G23.5 and PHEX-AS1 were significantly elevated in EpCAM-specific exosomes from lung cancer patients and could distinguish malignant from benign lung tumors. The amounts of RP11-77G23.5 were statistically higher in the subtype of lung adenocarcinoma (LUAC) than that of lung squamous cell carcinoma (LUSC), showing its capability to subtype LUAC and LUSC, while PHEX-AS1 exhibited distinct expression signatures between lower and higher tumor stages, and without and with distant metastasis, indicating its association with lung cancer progression. In conclusion, the EpCAM-specific exosomal lncRNAs RP11-77G23.5 and PHEX-AS1 may be promising diagnostic biomarkers for lung cancer. KEY MESSAGES: Serum EpCAM-positive exosomes promote lung cancer development in vitro and in vivo. Two EpCAM-specific exosomal lncRNAs can be simultaneously detected by RT-ddPCR. EpCAM-specific exosomal RP11-77G23.5 has the potential to subtype LUAC and LUSC. EpCAM-specific exosomal PHEX-AS1 is associated with lung cancer progression.
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http://dx.doi.org/10.1007/s00109-021-02145-4DOI Listing
January 2022

Prostate cancer-associated SPOP mutations lead to genomic instability through disruption of the SPOP-HIPK2 axis.

Nucleic Acids Res 2021 07;49(12):6788-6803

Department of Clinical Laboratory, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, China.

Speckle-type Poz protein (SPOP), an E3 ubiquitin ligase adaptor, is the most frequently mutated gene in prostate cancer. The SPOP-mutated subtype of prostate cancer shows high genomic instability, but the underlying mechanisms causing this phenotype are still largely unknown. Here, we report that upon DNA damage, SPOP is phosphorylated at Ser119 by the ATM serine/threonine kinase, which potentiates the binding of SPOP to homeodomain-interacting protein kinase 2 (HIPK2), resulting in a nondegradative ubiquitination of HIPK2. This modification subsequently increases the phosphorylation activity of HIPK2 toward HP1γ, and then promotes the dissociation of HP1γ from trimethylated (Lys9) histone H3 (H3K9me3) to initiate DNA damage repair. Moreover, the effect of SPOP on the HIPK2-HP1γ axis is abrogated by prostate cancer-associated SPOP mutations. Our findings provide new insights into the molecular mechanism of SPOP mutations-driven genomic instability in prostate cancer.
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http://dx.doi.org/10.1093/nar/gkab489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266658PMC
July 2021

LncRNA DPP10-AS1 promotes malignant processes through epigenetically activating its cognate gene DPP10 and predicts poor prognosis in lung cancer patients.

Cancer Biol Med 2021 Jun 9. Epub 2021 Jun 9.

Department of Biochemistry and Molecular Biology, Ningbo University School of Medicine, Ningbo 315211, China.

Objective: The purpose of this study was to explore the function and gene expression regulation of the newly identified lncRNA DPP10-AS1 in lung cancer, and its potential value as a prognostic biomarker.

Methods: qRT-PCR and Western blot were conducted to detect the expression of DDP10-AS1 and DPP10 in lung cancer cell lines and tissues. The effects of DDP10-AS1 on DPP10 expression, cell growth, invasion, apoptosis, and tumor growth were investigated in lung cancer cells by Western blot, rescue experiments, colony formation, flow cytometry, and xenograft animal experiments.

Results: The novel antisense lncRNA DPP10-AS1 was found to be highly expressed in cancer tissues ( < 0.0001), and its upregulation predicted poor prognosis in patients with lung cancer ( = 0.0025). Notably, DPP10-AS1 promoted lung cancer cell growth, colony formation, and cell cycle progression, and repressed apoptosis in lung cancer cells by upregulating DPP10 expression. Additionally, DPP10-AS1 facilitated lung tumor growth upregulation of DPP10 protein in a xenograft mouse model. Importantly, DPP10-AS1 positively regulated gene expression, and both were coordinately upregulated in lung cancer tissues. Mechanically, DPP10-AS1 was found to associate with mRNA but did not enhance mRNA stability. Hypomethylation of DPP10-AS1 and contributed to their coordinate upregulation in lung cancer.

Conclusions: These findings indicated that the upregulation of the antisense lncRNA DPP10-AS1 promotes lung cancer malignant processes and facilitates tumorigenesis by epigenetically regulating its cognate sense gene . DPP10-AS1 may serve as a candidate prognostic biomarker and a potential therapeutic target in lung cancer.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330531PMC
June 2021

Transcriptomic, proteomic, and physiological studies reveal key players in wheat nitrogen use efficiency under both high and low nitrogen supply.

J Exp Bot 2021 05;72(12):4435-4456

School of Biological Sciences, Washington State University, Pullman, WAUSA.

The effective use of available nitrogen (N) to improve crop grain yields provides an important strategy to reduce environmental N pollution and promote sustainable agriculture. However, little is known about the common genetic basis of N use efficiency (NUE) at varying N availability. Two wheat (Triticum aestivum L.) cultivars were grown in the field with high, moderate, and low N supply. Cultivar Zhoumai 27 outperformed Aikang 58 independent of the N supply and showed improved growth, canopy leaf area index, flag leaf surface area, grain number, and yield, and enhanced NUE due to both higher N uptake and utilization efficiency. Further, transcriptome and proteome analyses were performed using flag leaves that provide assimilates for grain growth. The results showed that many genes or proteins that are up- or down-regulated under all N regimes are associated with N and carbon metabolism and transport. This was reinforced by cultivar differences in photosynthesis, assimilate phloem transport, and grain protein/starch yield. Overall, our study establishes that improving NUE at both high and low N supply requires distinct adjustments in leaf metabolism and assimilate partitioning. Identified key genes/proteins may individually or concurrently regulate NUE and are promising targets for maximizing crop NUE irrespective of the N supply.
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http://dx.doi.org/10.1093/jxb/erab153DOI Listing
May 2021

Localization, Gene Expression, and Functions of Glutamine Synthetase Isozymes in Wheat Grain (.).

Front Plant Sci 2021 9;12:580405. Epub 2021 Feb 9.

Collaborative Innovation Center of Henan Grain Crops, College of Agronomy, Henan Agricultural University, Zhengzhou, China.

Glutamine synthetase (GS) plays a major role in plant nitrogen metabolism, but the roles of individual GS isoforms in grains are unknown. Here, the localization and expression of individual TaGS isozymes in wheat grain were probed with TaGS isoenzyme-specific antibodies, and the nitrogen metabolism of grain during the grain filling stage were investigated. Immunofluorescence revealed that TaGS1;1, TaGS1;3, and TaGS2 were expressed in different regions of the embryo. In grain transporting tissues, TaGS1;2 was localized in vascular bundle; TaGS1;2 and TaGS1;1 were in chalaza and placentochalaza; TaGS1;1 and TaGS1;3 were in endosperm transfer cells; and TaGS1;3 and TaGS2 were in aleurone layer. GS exhibited maximum activity and expression at 8 days after flowering (DAF) with peak glutamine content in grains; from then, increased largely from reduction, glutamate dehydrogenase (GDH) aminating activity increased continuously, and the activities of GS and glutamate synthase (GOGAT) decreased, while only TaGS1;3 kept a stable expression in different TaGS isozymes. Hence, GS-GOGAT cycle and GDH play different roles in assimilation of grain in different stages of grain development; TaGS1;3, located in aleurone layer and endosperm transfer cells, plays a key role in Gln into endosperm for gluten synthesis. At 30 DAF, grain amino acids are mainly transported from maternal phloem.
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http://dx.doi.org/10.3389/fpls.2021.580405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901976PMC
February 2021

Nitrogen Regulating the Expression and Localization of Four Glutamine Synthetase Isoforms in Wheat ( L.).

Int J Mol Sci 2020 Aug 31;21(17). Epub 2020 Aug 31.

Collaborative Innovation Center of Henan Grain Crops, College of Agronomy, Henan Agricultural University, Zhengzhou 450000, China.

Glutamine synthetase (GS), the key enzyme in plant nitrogen assimilation, is strictly regulated at multiple levels, but the most relevant reports focus on the mRNA level. Using specific antibodies as probes, the effects of nitrogen on the expression and localization of individual wheat GS (TaGS) isoforms were studied. In addition to TaGS2, TaGS1;1 with high affinity to substrate and TaGS1;3 with high catalytic activity were also localized in mesophyll, and may participate in cytoplasmic assimilation of ammonium (NH) released from photorespiration or absorbed by roots; TaGS1;2 was localized in xylem of leaves. In roots, although there were hundreds of times more than transcripts, the amount of TaGS1;1 subunit was not higher than that of TaGS1;2; NH inhibited TaGS1;1 expression but stimulated TaGS1;3 expression. In root tips, nitrate stimulated TaGS1;1, TaGS1;3, and TaGS2 expression in meristem, while NH promoted tissue differentiation and TaGS1;2 expression in endodermis and vascular tissue. Only TaGS1;2 was located in vascular tissue of leaves and roots, and was activated by glutamine, suggesting a role in nitrogen transport. TaGS1;3 was induced by NH in root endodermis and mesophyll, suggesting a function in relieving NH toxicity. Thus, TaGS isoforms play distinct roles in nitrogen assimilation for their different kinetic properties, tissue locations, and response to nitrogen regimes.
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http://dx.doi.org/10.3390/ijms21176299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504200PMC
August 2020

lncRNA JPX/miR-33a-5p/Twist1 axis regulates tumorigenesis and metastasis of lung cancer by activating Wnt/β-catenin signaling.

Mol Cancer 2020 01 15;19(1). Epub 2020 Jan 15.

Department of Biochemistry and Molecular Biology, Ningbo University School of Medicine, Ningbo, 315211, China.

Background: MicroRNAs (miRNAs) and Twist1-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination are well established, but the involvement of long noncoding RNAs (lncRNAs) in Twist1-mediated signaling remains largely unknown.

Methods: RT-qPCR and western blotting were conducted to detect the expression levels of lncRNA JPX and Twist1 in lung cancer cell lines and tissues. The impact of JPX on Twist1 expression, cell growth, invasion, apoptosis, and in vivo tumor growth were investigated in lung cancer cells by western blotting, rescue experiments, colony formation assay, flow cytometry, and xenograft animal experiment.

Results: We observed that lncRNA JPX was upregulated in lung cancer metastatic tissues and was closely correlated with tumor size and an advanced stage. Functionally, JPX promoted lung cancer cell proliferation in vitro and facilitated lung tumor growth in vivo. Additionally, JPX upregulated Twist1 by competitively sponging miR-33a-5p and subsequently induced EMT and lung cancer cell invasion. Interestingly, JPX and Twist1 were coordinately upregulated in lung cancer tissues and cells. Mechanically, the JPX/miR-33a-5p/Twist1 axis participated in EMT progression by activating Wnt/β-catenin signaling.

Conclusions: These findings suggest that lncRNA JPX, a mediator of Twist1 signaling, could predispose lung cancer cells to metastasis and may serve as a potential target for targeted therapy.
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http://dx.doi.org/10.1186/s12943-020-1133-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961326PMC
January 2020

CRL3-SPOP ubiquitin ligase complex suppresses the growth of diffuse large B-cell lymphoma by negatively regulating the MyD88/NF-κB signaling.

Leukemia 2020 05 27;34(5):1305-1314. Epub 2019 Nov 27.

Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.

Recurrent oncogenic mutations of MyD88 have been identified in a variety of lymphoid malignancies. Gain-of-function mutations of MyD88 constitutively activate downstream NF-κB signaling pathways, resulting in increased cellular proliferation and survival. However, whether MyD88 activity can be aberrantly regulated in MyD88-wild-type lymphoid malignancies remains poorly understood. SPOP is an adaptor protein of CUL3-based E3 ubiquitin ligase complex and frequently mutated genes in prostate and endometrial cancers. In this study, we reveal that SPOP binds to and induces the nondegradative ubiquitination of MyD88 by recognizing an atypical SPOP-binding motif in MyD88. This modification blocks Myddosome assembly and downstream NF-κB activation. SPOP is mutated in a subset of lymphoid malignancies, including diffuse large B-cell lymphoma (DLBCL). Lymphoid malignancies-associated SPOP mutants exhibited impaired binding to MyD88 and suppression of NF-κB activation. The DLBCL-associated, SPOP-binding defective mutants of MyD88 escaped from SPOP-mediated ubiquitination, and their effect on NF-κB activation is stronger than that of wild-type MyD88. Moreover, SPOP suppresses DLBCL cell growth in vitro and tumor xenograft in vivo by inhibiting the MyD88/NF-κB signaling. Therefore, SPOP acts as a tumor suppressor in DLBCL. Mutations in the SPOP-MyD88 binding interface may disrupt the SPOP-MyD88 regulatory axis and promote aberrant MyD88/NF-κB activation and cell growth in DLCBL.
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http://dx.doi.org/10.1038/s41375-019-0661-zDOI Listing
May 2020

Nutritional quality and health risks of wheat grains from organic and conventional cropping systems.

Food Chem 2020 Mar 11;308:125584. Epub 2019 Oct 11.

Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

The influence of cropping systems on nutrition and food safety is controversial. This study aimed to evaluate the effects of an organic cropping system (OCS) on wheat nutrition and food safety at the molecular level by using a comprehensive research method. Nutrient deviation in samples from an OCS and a conventional cropping system (CCS) were detected, and 58 biomarkers were selected through multivariate statistical analysis and were further qualitatively and quantitatively analyzed. The health risk of heavy metal(loid)s (HMs) for different populations was assessed based on the estimated average daily dose and recommended ingestion reference dose, which indicated that populations ingesting grains from OCSs had higher non-carcinogenic and carcinogenic risks. Additionally, HMs posed greater non-carcinogenic risks to children under five years old and greater carcinogenic risks to adults.This study highlights the need to consider the potential risk from HMs and nutritive ingredient differences in organic food.
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http://dx.doi.org/10.1016/j.foodchem.2019.125584DOI Listing
March 2020

Circulating Mitochondrial DNA is Linked to Progression and Prognosis of Epithelial Ovarian Cancer.

Transl Oncol 2019 Sep 2;12(9):1213-1220. Epub 2019 Jul 2.

Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address:

As peripheral blood contains fluctuated levels of circulating cell-free mitochondrial DNA (ccf mtDNA), we aimed to evaluate ccf mtDNA as a biomarker for diagnosis and prognosis of epithelial ovarian cancer (EOC). In the present study, we recruited 165 EOC patients and 60 healthy women. Quantitative RT-PCR was applied to amplify 79-bp and 230-bp fragments of the mitochondrial 16 s RNA gene in sera of these participants. MtDNA integrity was defined as the ratio of long to short mtDNA fragments. We observed that the levels of mtDNA79 and mtDNA230 were significantly increased (P = .0001), whereas the mtDNA integrity (P = .0001) was decreased in EOC patients compared with those in healthy controls. MtDNA79 showed a sensitivity of 90.3% and a specificity of 81.7% (AUC = 0.900) to discriminate EOC from healthy controls. Moreover, the amounts of mtDNA79 (P = .0001, P = .012, P = .039) and mtDNA230 (P = .0001, P = .042) continuously raised from healthy controls over FIGO I-II to FIGO III and IV, with highest levels of mtDNA79 (P = .0001) and mtDNA230 (P = .0001) in FIGO III and IV. Increasing levels of mtDNA79 (P = .003, P = .0001) and mtDNA230 (P = .041, P = .0001) were also associated with lymph node metastasis and CA125 values. The higher levels of mtDNA79 (P = .0001; HR 3.2, 95%CI:1.6-6.3) and mtDNA230 (borderline P = .048, HR 0.9, 95%CI:0.9-1.0) also correlated with poor patients' overall survival, of which mtDNA79 could act as an independent factor for overall survival. Our data show a significant association of increasing levels of ccf mtDNA with EOC progress and poor prognosis.
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http://dx.doi.org/10.1016/j.tranon.2019.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609736PMC
September 2019

Liquid biopsy: Circulating exosomal long noncoding RNAs in cancer.

Clin Chim Acta 2019 Aug 2;495:331-337. Epub 2019 May 2.

Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo 315211, China; Zhejiang Province Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China. Electronic address:

Despite many advances in diagnostics and multimodal treatment (surgery, radiotherapy, chemotherapy), cancer still remains one of the most important public health challenges worldwide because of the associated morbidity and mortality. Liquid biopsy has been developed to detect cancer at an early stage based on minimally invasive and serial body fluid tests with the advantage of following tumor evolution in real time. Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating cell-free noncoding RNAs (cfRNAs) and circulating exosomes represent the major components of liquid biopsy analysis. Liquid biopsy already has been implemented in cancer management, and most studies thus far are mainly focused on CTCs and ctDNA. In fact, the circulating long noncoding RNAs (lncRNAs) in exosomes have been discovered and confirmed to be closely related to tumorigenesis, metastasis and therapy. Thus this review is mainly focused on the clinical potential of circulating exosomal lncRNAs as a source of liquid biopsy biomarkers in cancer diagnosis, prognosis, and response to treatment, offering novel insights into the precision medicine of oncology.
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http://dx.doi.org/10.1016/j.cca.2019.04.082DOI Listing
August 2019

A two-miRNA signature (miR-33a-5p and miR-128-3p) in whole blood as potential biomarker for early diagnosis of lung cancer.

Sci Rep 2018 11 12;8(1):16699. Epub 2018 Nov 12.

Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, 315211, China.

MicroRNAs (MiRNAs) have been found to be dysregulated in lung cancer tissues compared to their matched paracancerous tissues. However, the roles of miRNAs in peripheral blood as potential biomarkers for early diagnosis of lung cancer remain poorly understood. Here we found that miR-33a-5p and miR-128-3p were down-regulated in lung cancer tissues and cell lines. The expression levels of miR-33a-5p and miR-128-3p in lung cancer tissues were significantly correlated to TNM stages. MiR-128-3p in lung cancer tissues was also remarkably related to smoking and tumor size. The relative expression levels of miR-33a-5p and miR-128-3p were positively correlated in lung cancer tissues. Notably, miR-33a-5p and miR-128-3p in whole blood of lung cancer patients or early-stage lung cancer patients (TNM stage I-II) were lowly expressed as compared with that in healthy controls. The receiver operating characteristic curve (ROC) analyses revealed higher area under the ROC curve (AUC) values and higher sensitivity/specificity of miR-33a-5p and miR-128-3p alone and in combination were superior to that of traditional tumor markers (CYFR21-1, NSE and CA72-4). Importantly, both miR-33a-5p and miR-128-3p in whole blood were highly stable even under different harsh conditions. The results demonstrate that tumor suppressor miR-33a-5p/miR-128-3p in whole blood can serve as novel biomarkers for the early detection of lung cancer.
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http://dx.doi.org/10.1038/s41598-018-35139-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232109PMC
November 2018

Circular RNAs Serve as Novel Biomarkers and Therapeutic Targets in Cancers.

Curr Gene Ther 2019 ;19(2):125-133

Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, China.

Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) that structurally form closed loops without 5'-end cap and 3'-end poly(A) tail unlike linear RNAs. CircRNAs are widely present in eukaryotic cells with the capabilities of structural stability, high abundance and cell- /tissue-specific expression. A growing body of researches suggest that the dysregulated circRNAs are intimately relevant to the occurrence and development of cancer. In this review, we mainly discuss the differentially expressed circRNAs in cancer tissues, plasma and exosomes, which makes it possible for clinicians to use certain circRNAs as novel biomarkers for cancer diagnosis and prognosis. In particular, we primarily focus on circRNAs as potential therapeutic targets, which will provide promising applications in cancer gene therapy.
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http://dx.doi.org/10.2174/1566523218666181109142756DOI Listing
July 2020

Nitrogen Supply and Leaf Age Affect the Expression of TaGS1 or TaGS2 Driven by a Constitutive Promoter in Transgenic Tobacco.

Genes (Basel) 2018 Aug 10;9(8). Epub 2018 Aug 10.

Collaborative Innovation Center of Henan Grain Crops, Henan Agriculture University, Zhengzhou 450000, China.

Glutamine synthetase (GS) plays a key role in nitrogen metabolism. Here, two types of tobacco transformants, overexpressing GS1 (TaGS1) or GS2 (TaGS2), were analysed. Four independent transformed lines, GS1-TR1, GS1-TR2, GS2-TR1 and GS2-TR2, were used for the nitrogen treatment. Under nitrogen-sufficient conditions, the leaves of GS2-TR showed high accumulation of the transcript, while those of GS1-TR showed a low transcript levels. However, compared with nitrogen-sufficient conditions, the transcript level increased in the leaves under nitrogen starvation, but the transcript level decreased. In addition, the and transcript levels were highest in the middle leaves under nitrogen-sufficient and starvation conditions. These results show that nitrogen supply and leaf age regulate expression, even when they are driven by a super-promoter. Additionally, in regard to nitrogen metabolism level, the lower leaves of the GS1-TR exhibited lower NH₄⁺ and higher amino acid contents, while the upper leaves exhibited higher amino acid, soluble protein and chlorophyll contents. The leaves of the GS2-TR exhibited lower NH₄⁺ but higher amino acid, soluble protein and chlorophyll contents. Given the role that GS isoforms play in nitrogen metabolism, these data suggest that overexpression may improve nitrogen transport, and that overexpression may improve nitrogen assimilation under nitrogen stress.
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http://dx.doi.org/10.3390/genes9080406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115907PMC
August 2018

Insights into the Noncoding RNA-encoded Peptides.

Protein Pept Lett 2018 ;25(8):720-727

Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, ZJ315211, China.

Background: Considerable evidence has indicated that most noncoding RNA (ncRNA) transcripts act directly as functional RNAs rather than as encoded peptides. However, a recent study of ribosome occupancy reported that many large intergenic ncRNAs (lincRNAs) are bound by ribosomes, raising the possibility that they are translated into proteins. These lincRNAs contain either Internal Ribosomal Entry Sites (IRES) or short Open Reading Frames (sORFs), and other translation elements, which can be translated into peptides with physiological functions.

Conclusion: This review discusses three major types of ncRNA-encoded peptides (ncPEPs). First, microRNA(miRNA)-encoded peptides (miPEPs) are translated from their primary transcripts of miRNA genes and can promote the development of plant roots. Second, a long ncRNA(lncRNA) containing sORF encodes a 90 residues long regulatory peptide. Upon the amino acid response, the lncRNA-encoded peptide reduces the activity of mammalian Target Rapamycin complex 1 (mTORC1) and promotes muscle regeneration. Third, a circular RNA (circRNA) of the Na+/Ca2+ exchanger gene 1 (NCX1) exon 2 transcript encodes a truncated NCX1 protein exhibiting the Na+/Ca2+ exchange activity. It is also of worth noting that the majority of ncRNAs is not translated. This review summarizes the current understanding of the translatability of ncRNAs and the functions of ncPEPs in cellular processes, which may provide novel insights into the roles of ncPEPs.
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http://dx.doi.org/10.2174/0929866525666180809142326DOI Listing
December 2018

Circulating lncRNA XLOC_009167 serves as a diagnostic biomarker to predict lung cancer.

Clin Chim Acta 2018 Nov 17;486:26-33. Epub 2018 Jul 17.

Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China. Electronic address:

Background: Long noncoding RNAs (lncRNAs) have been proven to be involved in carcinogenesis and to be released into peripheral blood. Our objective was to develop a circulating lncRNA as a novel biomarker to predict lung cancer.

Methods: We analyzed the lncRNA expression profile in lung cancer patients by lncRNA array and identified lncRNA XLOC_009167 as a circulating biomarker using qRT-PCR in whole blood of lung cancer patients. The diagnostic value of was analyzed by area under curve (AUC) and the receiver operating characteristic (ROC) test.

Results: LncRNA XLOC_009167 was screened as a candidate biomarker for lung cancer and was up-regulated in both lung cancer tissues and cell lines. Notably, lncRNA XLOC_009167 in whole blood of lung cancer patients was highly expressed as compared with that in healthy controls or in patients with pneumonia. The values of AUC of lung cancer vs. healthy controls, and that of lung cancer vs. pneumonia were 0.7398 (95%CI = 0.6493 to 0.8303) and 0.7005 (95%CI = 0.5771 to 0.8240), respectively. Intriguingly, the ROC showed lncRNA XLOC_009167 was a better diagnostic potential compared to the traditional biomarkers (CYFR21-1, NSE and CA72-4), and the circulating lncRNA XLOC_009167 was found to be stable in whole blood under different conditions.

Conclusions: LncRNA XLOC_009167 could serve as a novel diagnostic biomarker to distinguish lung cancer from benign lung disease and healthy controls.
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http://dx.doi.org/10.1016/j.cca.2018.07.026DOI Listing
November 2018

CRISPR/Cas9-mediated noncoding RNA editing in human cancers.

RNA Biol 2018 01 9;15(1):35-43. Epub 2017 Nov 9.

a Department of Biochemistry and Molecular Biology , Medical School of Ningbo University , Ningbo , Zhejiang , China.

Cancer is characterized by multiple genetic and epigenetic alterations, including a higher prevalence of mutations of oncogenes and/or tumor suppressors. Mounting evidences have shown that noncoding RNAs (ncRNAs) are involved in the epigenetic regulation of cancer genes and their associated pathways. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) system, a revolutionary genome-editing technology, has shed light on ncRNA-based cancer therapy. Here, we briefly introduce the classifications and mechanisms of CRISPR/Cas9 system. Importantly, we mainly focused on the applications of CRISPR/Cas9 system as a molecular tool for ncRNA (microRNA, long noncoding RNA and circular RNA, etc.) editing in human cancers, and the novel techniques that are based on CRISPR/Cas9 system. Additionally, the off-target effects and the corresponding solutions as well as the challenges toward CRISPR/Cas9 were also evaluated and discussed. Long- and short-ncRNAs have been employed as targets in precision oncology, and CRISPR/Cas9-mediated ncRNA editing may provide an excellent way to cure cancer.
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http://dx.doi.org/10.1080/15476286.2017.1391443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785983PMC
January 2018

Pecanex functions as a competitive endogenous RNA of S-phase kinase associated protein 2 in lung cancer.

Cancer Lett 2017 10 5;406:36-46. Epub 2017 Aug 5.

Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, ZJ 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, ZJ 315211, China. Electronic address:

Investigating the RNA-RNA interactions involving in the initiation and progression of non-small cell lung cancer (NSCLC) may provide promising diagnostic and targeted therapeutic strategies. Here, we showed that pecanex (PCNX) positively regulates the mRNA and protein expressions of S-phase kinase associated protein 2 (Skp2) in miRNA- and 3' UTR-dependent manners. And miR-26, miR-182, miR-340 and miR-506 were verified as the common miRNAs shared by Skp2 and PCNX. Intriguingly, we initially uncovered that PCNX-3' UTR promotes cell growth, proliferation and cell cycle progression, and suppresses apoptosis of lung cancer cells, which is consistent with the oncogenic activity of Skp2-3' UTR. Consequently, PCNX was identified as a competitive endogenous RNA (ceRNA) of Skp2. Moreover, knockdown of PCNX inhibits EGF-induced Akt phosphorylation, which can be reversed by the silencing of Dicer. Finally, we further discovered that Skp2 and PCNX are coordinately upregulated in lung cancer tissues compared with the adjacent non-tumor tissues. Our study establishes for the first time the oncogenic property of PCNX-3' UTR and Skp2-3' UTR, and the PCNX-miRNA-Skp2 regulatory pattern, which may offer a molecular basis for the diagnosis and targeted therapy in NSCLC.
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http://dx.doi.org/10.1016/j.canlet.2017.07.030DOI Listing
October 2017

The role of glutamine synthetase isozymes in enhancing nitrogen use efficiency of N-efficient winter wheat.

Sci Rep 2017 04 20;7(1):1000. Epub 2017 Apr 20.

Collaborative Innovation Center of Henan Grain Crops, Henan Agricultural University, Zhengzhou, 450002, China.

Glutamine synthetase (GS) isozymes play critical roles in nitrogen (N) metabolism. However, the exact relationship between GS and nitrogen use efficiency (NUE) remain unclear. We have selected and compared two wheat cultivars, YM49 and XN509, which were identified as the N-efficient and N-inefficient genotypes, respectively. In this study, agronomical, morphological, physiological and biochemical approaches were performed. The results showed that TaGS1 was high expressed post-anthesis, and TaGS2 was highly expressed pre-anthesis in N-efficient genotype compared to N-inefficient genotype. GS1 and GS2 isozymes were also separated by native-PAGE and found that the spatial and temporal distribution of GS isozymes, their expression of gene and protein subunits in source-sink-flow organs during development periods triggered the pool strength and influenced the N flow. According to the physiological role of GS isozymes, we illustrated four metabolic regulation points, by which acting collaboratively in different organs, accelerating the transport of nutrients to the grain. It suggested that the regulation of GS isozymes may promote flow strength and enhance NUE by a complex C-N metabolic mechanism. The relative activity or amount of GS1 and GS2 isozymes could be a potential marker to predict and select wheat genotypes with enhanced NUE.
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http://dx.doi.org/10.1038/s41598-017-01071-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430530PMC
April 2017

Circulating Cell-Free miR-373, miR-200a, miR-200b and miR-200c in Patients with Epithelial Ovarian Cancer.

Adv Exp Med Biol 2016 ;924:3-8

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg-Eppendorf, 20246, Germany.

In the present study, we investigated whether circulating cell-free microRNAs serve as potential biomarkers in epithelial ovarian cancer (EOC) patients. Circulating miR-373, miR-200a, miR-200b and miR-200c were quantified in a cohort of 60 EOC patients, 20 patients with benign ovarian diseases and 32 healthy women using quantitative TaqMan MicroRNA assays. The serum concentrations of cell-free miR-373, miR-200a, miR-200b and miR-200c were significantly higher in EOC patients than in healthy women (p = 0.0001). With a sensitivity of 83 % and a specificity of 100 %, the combination of miR-200a, miR-200b and miR-200c could differ between malignant and benign ovarian tumors (p = 0.0001). Elevated levels of these cell-free microRNAs could be detected in FIGO I-II and FIGO III-IV stages, grading G1-2 and G3 and lymph node-negative and -positive EOC. In conclusion, the increased serum levels of this microRNA panel have diagnostic value for distinguishing healthy controls and benign tumors from EOC.
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http://dx.doi.org/10.1007/978-3-319-42044-8_1DOI Listing
September 2017

Diagnostic and prognostic relevance of circulating exosomal miR-373, miR-200a, miR-200b and miR-200c in patients with epithelial ovarian cancer.

Oncotarget 2016 Mar;7(13):16923-35

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany.

Exosomes are membrane vesicles that mediate intercellular communication by transporting their molecular cargo from cell to cell. We investigated whether serum levels of exosomal miR-373, miR-200a, miR-200b and miR-200c and circulating exosomes have diagnostic and prognostic relevance in a cohort of 163 epithelial ovarian cancer (EOC) patients using TaqMan MicroRNA assays and ELISA. The serum concentrations of exosomal miR-373 (p = 0.0001), miR-200a (p = 0.0001), miR-200b (p = 0.0001) and miR-200c (p = 0.028) were significantly higher in EOC patients than healthy women. The levels of miR-200a (p = 0.0001), miR-200b (p = 0.0001) and miR-200c (p = 0.019) could distinguish between malignant and benign ovarian tumors. While the levels of miR-373 and miR-200a were increased in all FIGO/lymph node stages (p = 0.0001), the levels of miR-200b and miR-200c were higher in patients with FIGO stage III-IV (p = 0.0001, p = 0.008, respectively) including lymph node metastasis (p = 0.0001, p = 0.004, respectively) than FIGO stages I-II. The increased levels of miR-200b and miR-200c were also associated with CA125 values (p = 0.0001, p = 0.0001, respectively) and a shorter overall survival (p = 0.007, p = 0.017, respectively). The levels of exosomes were excessively elevated in EOC patients (p = 0.0001). In all three cohorts, they were positively associated with the serum levels of exosomal miR-373 (p = 0.004), miR-200a (p = 0.0001), miR-200b (p = 0.0001) and miR-200c (p = 0.008). In conclusion, the increased levels of exosomal miR-200b and miR-200c mainly observed in advanced EOC suggest that these microRNAs may be involved in tumor progression. The high concentrations of exosomes in EOC patients imply an excessive, active exosomal secretion in EOC.
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http://dx.doi.org/10.18632/oncotarget.7850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941360PMC
March 2016

Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients.

Br J Cancer 2015 Nov 22;113(9):1358-66. Epub 2015 Sep 22.

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.

Background: Owing to late diagnosis in advanced disease stages, prognosis of patients with epithelial ovarian cancer (EOC) is poor. The quantification of deregulated levels of microRNAs could facilitate earlier diagnosis and improve prognosis of EOC.

Methods: Seven microRNAs (miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429) were quantified in the serum of 180 EOC patients and 66 healthy women by TaqMan PCR microRNA assays. Median follow-up time was 21 months. The effects of miR-7 and miR-429 on apoptosis, cell proliferation, migration and invasion were investigated in two (EOC) cell lines.

Results: Serum levels of miR-25 (P=0.0001) and miR-93 (P=0.0001) were downregulated, whereas those of miR-7 (P=0.001) and miR-429 (P=0.0001) were upregulated in EOC patients compared with healthy women. The four microRNAs discriminated EOC patients from healthy women with a sensitivity of 93% and a specificity of 92%. The levels of miR-429 positively correlated with CA125 values (P=0.0001) and differed between FIGO I-II and III-IV stages (P=0.001). MiR-429 was an independent predictor of overall survival (P=0.011). Overexpressed miR-429 in SKOV3 cells led to suppression of cell migration (P=0.037) and invasion (P=0.011). Increased levels of miR-7 were associated with lymph node metastases (P=0.0001) and FIGO stages III-IV (P=0.0001). Overexpressed miR-7 in SKOV3 cells resulted in increased cell migration (P=0.001) and invasion (P=0.011). Additionally, the increased levels of miR-376a correlated with FIGO stages III-IV (P=0.02).

Conclusions: Our data indicate the diagnostic potential of miR-7, miR-25, miR-93 and miR-429 in EOC and the prognostic potential of miR-429. This microRNA panel may be promising molecules to be targeted in the treatment of EOC.
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http://dx.doi.org/10.1038/bjc.2015.340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815782PMC
November 2015

Characterization and subcellular localization of two 14-3-3 genes and their response to abiotic stress in wheat.

Sheng Wu Gong Cheng Xue Bao 2014 Feb;30(2):232-46

In order to investigate biological functions of the 14-3-3 genes and their response to abiotic stress, two cDNAs (designated as Ta14R1 and Ta14R2) encoding putative 14-3-3 proteins were isolated from wheat by PCR and rapid amplification of cDNA end (RACE) technique. The cDNA of Ta14R1 is 999bp and encodes a protein of 262 amino acids, while the cDNA of Ta14R2 is 897bp in length and encodes a protein of 261 amino acids. Transient expression assays using Ta14R1/Ta14R2-GFP fusion constructs indicated that Ta14R1 and Ta14R2 were located in cytoplasm and cell membrane but not in chloroplasts. Real-time quantitative (RT-PCR) analysis revealed that Ta14R1 and Ta14R2 were differentially expressed in wheat tissues and significantly up-regulated in roots and shoots 1d after germination, indicating they may play a role in process of seed germination. The expression of the two genes in roots and leaves were significantly induced by plant hormone ABA, as well as heat, cold and drought treatments, suggesting that the two 14-3-3 genes in wheat may be involved in ABA dependent stress-responding pathway and response to heat, cold and drought stress.
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February 2014
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