Publications by authors named "Qiqiang Guo"

22 Publications

  • Page 1 of 1

The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis.

Sci Adv 2021 Feb 24;7(9). Epub 2021 Feb 24.

Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35249-7331, USA.

Improper distribution of chromosomes during mitosis can contribute to malignant transformation. Higher eukaryotes have evolved a mitotic catastrophe mechanism for eliminating mitosis-incompetent cells; however, the signaling cascade and its epigenetic regulation are poorly understood. Our analyses of human cancerous tissue revealed that the NAD-dependent deacetylase SIRT2 is up-regulated in early-stage carcinomas of various organs. Mass spectrometry analysis revealed that SIRT2 interacts with and deacetylates the structural maintenance of chromosomes protein 1 (SMC1A), which then promotes SMC1A phosphorylation to properly drive mitosis. We have further demonstrated that inhibition of SIRT2 activity or continuously increasing SMC1A-K579 acetylation causes abnormal chromosome segregation, which, in turn, induces mitotic catastrophe in cancer cells and enhances their vulnerability to chemotherapeutic agents. These findings suggest that regulation of the SIRT2-SMC1A axis through deacetylation-phosphorylation permits escape from mitotic catastrophe, thus allowing early precursor lesions to overcome oncogenic stress.
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http://dx.doi.org/10.1126/sciadv.abe5518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904255PMC
February 2021

The Regulatory Effect of SIRT1 on Extracellular Microenvironment Remodeling.

Int J Biol Sci 2021 1;17(1):89-96. Epub 2021 Jan 1.

College of Basic Medical Science, Institute of Translational Medicine, Key Laboratory of Medical Cell Biology, Ministry of Education, Key Laboratory of Liaoning Province, China Medical University, Shenyang, Liaoning Province, P.R. China, 110122.

The sirtuins family is well known by its unique nicotinamide adenine dinucleotide (NAD)-dependent deacetylase function. The most-investigated member of the family, Sirtuin 1 (SIRT1), accounts for deacetylating a broad range of transcription factors and coregulators, such as p53, the Forkhead box O (FOXO), and so on. It serves as a pivotal regulator in various intracellular biological processes, including energy metabolism, DNA damage response, genome stability maintenance and tumorigenesis. Although the most attention has been focused on its intracellular functions, the regulatory effect on extracellular microenvironment remodeling of SIRT1 has been recognized by researchers recently. SIRT1 can regulate cell secretion process and participate in glucose metabolism, neuroendocrine function, inflammation and tumorigenesis. Here, we review the advances in the understanding of SIRT1 on remodeling the extracellular microenvironment, which may provide new ideas for pathogenesis investigation and guidance for clinical treatment.
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http://dx.doi.org/10.7150/ijbs.52619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757024PMC
January 2021

Hypoxia-autophagy axis induces VEGFA by peritoneal mesothelial cells to promote gastric cancer peritoneal metastasis through an integrin α5-fibronectin pathway.

J Exp Clin Cancer Res 2020 Oct 20;39(1):221. Epub 2020 Oct 20.

Institute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, 110001, Liaoning, China.

Background: Peritoneal metastasis (PM) is an important pathological process in the progression of gastric cancer (GC). The metastatic potential of tumor and stromal cells is governed by hypoxia, which is a key molecular feature of the tumor microenvironment. Mesothelial cells also participate in this complex and dynamic process. However, the molecular mechanisms underlying the hypoxia-driven mesothelial-tumor interactions that promote peritoneal metastasis of GC remain unclear.

Methods: We determined the hypoxic microenvironment in PM of nude mice by immunohistochemical analysis and screened VEGFA by human growth factor array kit. The crosstalk mediated by VEGFA between peritoneal mesothelial cells (PMCs) and GC cells was determined in GC cells incubated with conditioned medium prepared from hypoxia-treated PMCs. The association between VEGFR1 and integrin α5 and fibronectin in GC cells was enriched using Gene Set Enrichment Analysis and KEGG pathway enrichment analysis. In vitro and xenograft mouse models were used to evaluate the impact of VEGFA/VEGFR1 on gastric cancer peritoneal metastasis. Confocal microscopy and immunoprecipitation were performed to determine the effect of hypoxia-induced autophagy.

Results: Here we report that in the PMCs of the hypoxic microenvironment, SIRT1 is degraded via the autophagic lysosomal pathway, leading to increased acetylation of HIF-1α and secretion of VEGFA. Under hypoxic conditions, VEGFA derived from PMCs acts on VEGFR1 of GC cells, resulting in p-ERK/p-JNK pathway activation, increased integrin α5 and fibronectin expression, and promotion of PM.

Conclusions: Our findings have elucidated the mechanisms by which PMCs promote PM in GC in hypoxic environments. This study also provides a theoretical basis for considering autophagic pathways or VEGFA as potential therapeutic targets to treat PM in GC.
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http://dx.doi.org/10.1186/s13046-020-01703-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576728PMC
October 2020

RNF8 induces β-catenin-mediated c-Myc expression and promotes colon cancer proliferation.

Int J Biol Sci 2020 1;16(12):2051-2062. Epub 2020 May 1.

Department of Anorectal Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, RP China.

DNA damage signals transducer RING finger protein 8 (RNF8) is involved in maintaining genomic stability by facilitating the repair of DNA double-strand breaks (DSB) via ubiquitin signaling. By analyzing the TCGA database and colon cancer tissue microarrays, we found that the expression level of RNF8 was positively correlated with that of c-Myc in colon cancer, which were closely associated with poor survival of colon cancer patients. Furthermore, overexpressing and knocking down RNF8 increased and decreased the expression of c-Myc in colon cancer cells, respectively. In addition, RNF8 interacted with β-catenin and facilitated its nuclear translocation by conjugating K63 polyubiquitination on it. These observations suggested a de novo role of RNF8 in promoting the progression of colon cancer by inducing β-catenin-mediated c-Myc expression.
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http://dx.doi.org/10.7150/ijbs.44119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294952PMC
May 2020

Septin4 promotes cell death in human colon cancer cells by interacting with BAX.

Int J Biol Sci 2020 7;16(11):1917-1928. Epub 2020 Apr 7.

Key Laboratory of Medical Cell Biology, Ministry of Education; Institute of Translational Medicine, Collegeof Medical Science, China Medical University; Liaoning Province, Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang, Liaoning Province, China.

Septin4 is a tumor suppressor protein that promotes cell programmed death in various cell types through specifically antagonizing XIAP (X linked inhibitor of apoptosis), little is known its other novel binding partner and role in colorectal cancer. In this study, we found that Septin4 significantly expressed lower in human colon cancer when compared to peri-tumor benign cells, and its low expression was significantly associated with worse prognostic outcomes. Furthermore, Septin4 participated in DOX-induced colon cancer cell death . Septin4-overexpressing colon cancer cells displayed augmented apoptotic cell death and ROS production. Additionally, Septin4-knockdown cells revealed a resistance of DOX-induced cell death and reduced ROS production. Importantly, we first identified that BAX is a novel Septin4 binding partner and the interaction is enhanced under DOX treatment. Finally, Septin4-knockdown promoted colon cells growth . These observations suggest that Septin4 as an essential molecule contribute to the occurrence and development of human colon cancer and provide new technical approaches for targeted treatment of this disease.
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http://dx.doi.org/10.7150/ijbs.44429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211164PMC
April 2020

Long-reads reveal that plastid genome contains extensive repeat sequences, and recombination exists among plastid genomes of photosynthetic Ericaceae.

PeerJ 2020 22;8:e9048. Epub 2020 Apr 22.

College of Agriculture, Guizhou University, Guiyang, Guizhou, China.

Background: Franch. var. delavayi is a wild ornamental plant species in Guizhou Province, China. The lack of its plastid genome information seriously hinders the further application and conservation of the valuable resource.

Methods: The complete plastid genome of was assembled from long sequence reads. The genome was then characterized, and compared with those of other photosynthetic Ericaceae species.

Results: The plastid genome of has a typical quadripartite structure, and a length of 202,169 bp. It contains a large number of repeat sequences and shows preference for codon usage. The comparative analysis revealed the irregular recombination of gene sets, including rearrangement and inversion, in the large single copy region. The extreme expansion of the inverted repeat region shortened the small single copy, and expanded the full length of the genome. In addition, consistent with traditional taxonomy, with nine other species of the same family were clustered into Ericaceae based on the homologous protein-coding sequences of the plastid genomes. Thus, the long-read assembly of the plastid genome of would provide basic information for the further study of the evolution, genetic diversity, and conservation of and its relatives.
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http://dx.doi.org/10.7717/peerj.9048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183307PMC
April 2020

Involvement of SAMHD1 in dNTP homeostasis and the maintenance of genomic integrity and oncotherapy (Review).

Int J Oncol 2020 Apr 14;56(4):879-888. Epub 2020 Feb 14.

College of Basic Medical Science, Institute of Translational Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.

Sterile alpha motif and histidine/aspartic acid domain‑containing protein 1 (SAMHD1), the only deoxynucleotide triphosphate (dNTP) hydrolase in eukaryotes, plays a crucial role in regulating the dynamic balance and ratio of cellular dNTP pools. Furthermore, SAMHD1 has been reported to be involved in the pathological process of several diseases. Homozygous SAMHD1 mutations have been identified in immune system disorders, such as autoimmune disease Aicardi‑Goutières syndrome (AGS), whose primary pathogenesis is associated with the abnormal accumulation and disproportion of dNTPs. SAMHD1 is also considered to be an intrinsic virus‑restriction factor by suppressing the viral infection process, including reverse transcription, replication, packaging and transmission. In addition, SAMHD1 has been shown to promote genome integrity during homologous recombination following DNA damage, thus being considered a promising candidate for oncotherapy applications. The present review summarizes the molecular mechanisms of SAMHD1 regarding the regulation of dNTP homeostasis and DNA damage response. Additionally, its potential effects on tumorigenesis and oncotherapy are reported.
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http://dx.doi.org/10.3892/ijo.2020.4988DOI Listing
April 2020

Accumulation of prelamin A induces premature aging through mTOR overactivation.

FASEB J 2020 06 13;34(6):7905-7914. Epub 2020 Apr 13.

Institute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.

Hutchinson-Gilford progeria syndrome (HGPS) arises when a truncated form of farnesylated prelamin A accumulates at the nuclear envelope, leading to misshapen nuclei. Previous studies of adult Zmpste24-deficient mice, a mouse model of progeria, have reported a metabolic response involving inhibition of the mTOR (mammalian target of rapamycin) kinase and activation of autophagy. However, exactly how mTOR or autophagy is involved in progeria remains unclear. Here, we investigate this question by crossing Zmpste24 mice with mice hypomorphic in mTOR (mTOR ), or mice heterozygous in autophagy-related gene 7 (Atg7 ). We find that accumulation of prelamin A induces premature aging through mTOR overactivation and impaired autophagy in newborn Zmpste24 mice. Zmpste24 mice with genetically reduced mTOR activity, but not heterozygosity in Atg7, show extended lifespan. Moreover, mTOR inhibition partially restores autophagy and S6K1 activity. We also show that progerin interacts with the Akt phosphatase to promote full activation of the Akt/mTOR signaling pathway. Finally, although we find that genetic reduction of mTOR postpones premature aging in Zmpste24 KO mice, frequent embryonic lethality occurs. Together, our findings show that over-activated mTOR contributes to premature aging in Zmpste24 mice, and suggest a potential strategy in treating HGPS patients with mTOR inhibitors.
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http://dx.doi.org/10.1096/fj.201903048RRDOI Listing
June 2020

Competing endogenous RNA (ceRNA) hypothetic model based on comprehensive analysis of long non-coding RNA expression in lung adenocarcinoma.

PeerJ 2019 7;7:e8024. Epub 2019 Nov 7.

Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning, China.

Background: Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer with high malignancy and bad prognosis, consisted of lung adenocarcinomas (LUAD) and lung squamous cell carcinomas (LUSC) chiefly. Multiple studies have indicated that competing endogenous RNA (ceRNA) network centered long noncoding RNAs (lncRNAs) can regulate gene expression and the progression of various cancers. However, the research about lncRNAs-mediated ceRNA network in LUAD is still lacking.

Methods: In this study, we analyzed the RNA-seq database from The Cancer Genome Atlas (TCGA) and obtained dysregulated lncRNAs in NSCLC, then further identified survival associated lncRNAs through Kaplan-Meier analysis. Quantitative real time PCR (qRT-PCR) was performed to confirm their expression in LUAD tissues and cell lines. The ceRNA networks were constructed based on DIANA-TarBase and TargetScan databases and visualized with OmicShare tools. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to investigate the potential function of ceRNA networks.

Results: In total, 1,437 and 1,699 lncRNAs were found to be up-regulated in LUAD and LUSC respectively with 895 lncRNAs overlapping (|log2FC| > 3, adjusted value <0.01). Among which, 222 lncRNAs and 46 lncRNAs were associated with the overall survival (OS) of LUAD and LUSC, and 18 out of 222 up-regulated lncRNAs were found to have inverse correlation with LUAD patients' OS (|log2FC| > 3, adjusted value < 0.02). We selected 3 lncRNAs (CASC8, LINC01842 and VPS9D1-AS1) out of these 18 lncRNAs and confirmed their overexpression in lung cancer tissues and cells. CeRNA networks were further constructed centered CASC8, LINC01842 and VPS9D1-AS1 with 3 miRNAs and 100 mRNAs included respectively.

Conclusion: Through comprehensively analyses of TCGA, our study identified specific lncRNAs as candidate diagnostic and prognostic biomarkers for LUAD. The novel ceRNA network we created provided more insights into the regulatory mechanisms underlying LUAD.
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http://dx.doi.org/10.7717/peerj.8024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842565PMC
November 2019

SIRT1 modulates cell cycle progression by regulating CHK2 acetylation-phosphorylation.

Cell Death Differ 2020 02 17;27(2):482-496. Epub 2019 Jun 17.

Institute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, No. 77, Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China.

Both the stress-response protein, SIRT1, and the cell cycle checkpoint kinase, CHK2, play critical roles in aging and cancer via the modulation of cellular homeostasis and the maintenance of genomic integrity. However, the underlying mechanism linking the two pathways remains elusive. Here, we show that SIRT1 functions as a modifier of CHK2 in cell cycle control. Specifically, SIRT1 interacts with CHK2 and deacetylates it at lysine 520 residue, which suppresses CHK2 phosphorylation, dimerization, and thus activation. SIRT1 depletion induces CHK2 hyperactivation-mediated cell cycle arrest and subsequent cell death. In vivo, genetic deletion of Chk2 rescues the neonatal lethality of Sirt1 mice, consistent with the role of SIRT1 in preventing CHK2 hyperactivation. Together, these results suggest that CHK2 mediates the function of SIRT1 in cell cycle progression, and may provide new insights into modulating cellular homeostasis and maintaining genomic integrity in the prevention of aging and cancer.
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http://dx.doi.org/10.1038/s41418-019-0369-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206007PMC
February 2020

The Functions of DNA Damage Factor RNF8 in the Pathogenesis and Progression of Cancer.

Int J Biol Sci 2019 9;15(5):909-918. Epub 2019 Mar 9.

Institute of Translational Medicine, China Medical University; Key Laboratory of Medical Cell Biology, Ministry of Education; Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang, Liaoning Province, China.

The really interesting new gene (RING) finger protein 8 (RNF8) is a central factor in DNA double strand break (DSB) signal transduction. DSB damage is the most toxic type of DNA damage to cells and is related to genomic instability. Multiple roles for RNF8 have been identified in DNA damage response as well as in other functions, such as telomere protection, cell cycle control and transcriptional regulation. These functions are closely correlated to tumorigenesis and cancer progression. Indeed, deficiency of RNF8 caused spontaneous tumorigenesis in a mouse model. Deciphering these mechanisms of RNF8 may shed light on strategies for cancer treatment. In this review, we summarize the current understanding of both classical and nonclassical functions of RNF8, and discuss its roles in the pathogenesis and progression of tumor.
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http://dx.doi.org/10.7150/ijbs.31972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535783PMC
March 2020

Genetic diversity and population structure of two endemic (Cupressaceae) species on the Qinghai-Tibetan plateau.

J Genet 2019 03;98

Tibet Agricultural and Animal Husbandry College, Nyingchi 860000, Tibet, People's Republic of China.

and are ecologically and economically important endemic species of the conifer family Cupressaceae on the Qinghai-Tibetan plateau. was previously classified as a subspecies of because of their similar morphological characteristics and close distribution. In this study, 401 individuals were sampled from 16 populations of the two species. The specimens were genotyped using 10 polymorphic microsatellite loci through fluorescence polymerase chain reaction (PCR). The genetic diversity of and populations was generally low, with the highest genetic diversity detected in the population LLS of . Distance-based phylogenetic and principal co-ordinates analyses indicated a clear genetic structures for the 16 populations of the two species. Moreover, Mantel test results showed indistinctive correlations between population-pairwise F values and geographic distances, as well as between genetic distances and geographic distances in and , respectively. AMOVA suggested that genetic variation mostly resided within populations. Sixteen naturalpopulations were evidently clustered into two major groups in the constructed neighbour-joining tree. The results demonstrated that and are different species. The genetic information provided important theoretical references for conservation and management of the two endangered Cupressus species.
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March 2019

Autophagy resists EMT process to maintain retinal pigment epithelium homeostasis.

Int J Biol Sci 2019 1;15(3):507-521. Epub 2019 Jan 1.

Key Laboratory of Medical Cell Biology, Ministry of Education; Institute of Translational Medicine, China Medical University; Liaoning Province, Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang, Liaoning Province, 110122, China.

Proliferative vitreoretinopathy (PVR) is the most serious fibrous complication that causes vision loss after intraocular surgery, and there is currently no effective treatment in clinical. Autophagy is an important cell biological mechanism in maintaining the homeostasis of tissues and cells, resisting the process of EMT. However, it is still unclear whether autophagy could resist intraocular fibrosis and prevent PVR progression. In this study, we investigated the expression of mesenchymal biomarkers in autophagy deficiency cells and found these proteins were increased. The mesenchymal protein transcription factor Twist can bind to autophagy related protein p62 and promote the degradation of Twist, which reduced the expression of mesenchymal markers. By constructing an EMT model of retinal pigment epithelial (RPE) cells in vitro, we found that autophagy was activated in the EMT process of RPE cells. Moreover, in autophagy deficient RPE cell line via knockdown autophagy related protein 7 (Atg7), the expression of epithelial marker claudin-1 was suppressed and the mesenchymal markers were increased, accompanied by an increase in cell migration and contractility. Importantly, RPE epithelial properties can be maintained by promoting autophagy and effectively reversing TFG-β2-induced RPE fibrosis. These observations reveal that autophagy may be an effective way to treat PVR.
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http://dx.doi.org/10.7150/ijbs.30575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367589PMC
January 2020

Atg7 inhibits Warburg effect by suppressing PKM2 phosphorylation resulting reduced epithelial-mesenchymal transition.

Int J Biol Sci 2018 12;14(7):775-783. Epub 2018 May 12.

Key Laboratory of Medical Cell Biology, Ministry of Education; Institute of Translational Medicine, China Medical University; Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang, Liaoning Province, China.

Metabolic reprogramming is a distinct hallmark in tumorigenesis. Autophagy can rewire cell metabolism by regulating intracellular homeostasis. Warburg effect is a specific energy metabolic process that allows tumor cells to metabolize glucose via glycolysis into lactate even in the presence of oxygen. Although both autophagy and Warburg effect are involved in the stress response to energy crisis in tumor cells, their molecular relationship has remained largely elusive. We found that Atg7, a key molecule involved in autophagy, inhibits the Warburg effect. Mechanistically, Atg7 binds PKM2 and prevents its Tyr-105 phosphorylation by FGFR1. Furthermore, the hyperphosphorylation of PKM2 and its induced Warburg effect due to Atg7 deficiency promote epithelial-mesenchymal transition (EMT). Conversely, overexpression of Atg7 inhibits PKM2 phosphorylation and the Warburg effect, thereby inhibiting EMT of tumor cells. Our work reveals a molecular link between Atg7 and the Warburg effect, which may provide insight into novel strategies for cancer treatment.
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http://dx.doi.org/10.7150/ijbs.26077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001680PMC
July 2019

Therapeutic potential of a dual mTORC1/2 inhibitor for the prevention of posterior capsule opacification: An in vitro study.

Int J Mol Med 2018 Apr 18;41(4):2099-2107. Epub 2018 Jan 18.

Department of Ophthalmology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Mammalian target of rapamycin (mTOR) serves a central role in regulating cell growth and survival, and has been demonstrated to be involved in the pathological progression of posterior capsule opacification (PCO). In the present study, the potency of PP242, a novel dual inhibitor of mTOR complex 1/2 (mTORC1/2), in the suppression of the growth of human lens epithelial cells (HLECs) was investigated. Using a Cell Counting Kit‑8 and a wound healing assay, it was demonstrated that PP242 inhibited the proliferation and migration of HLECs. In addition, western blot analysis indicated that PP242 completely inhibited mTORC1 and mTORC2 downstream signaling activities, whereas rapamycin only partially inhibited mTORC1 activity within LECs. Furthermore, PP242 treatment led to an upregulation of the expression levels of p53 and B cell lymphoma‑2 (Bcl‑2)‑associated X and downregulation of Bcl‑2. In addition, flow cytometric analysis demonstrated that PP242 induced the cell cycle arrest at the G0/G1 phase, which may have caused apoptosis and induced autophagy within the LECs. The results of the present study suggested that administration of PP242 may potentially offer a novel therapeutic approach for the prevention of PCO.
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http://dx.doi.org/10.3892/ijmm.2018.3398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810205PMC
April 2018

P21-activated kinase 4 involves TSH induced papillary thyroid cancer cell proliferation.

Oncotarget 2017 Apr;8(15):24882-24891

Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, P.R. China.

Papillary thyroid cancer is a common endocrine malignancy. Although p21-activated kinase 4 (PAK4) is involved in the development of different types of tumor, its function has not been investigated in papillary thyroid cancer. Here, we identified a role for PAK4 in papillary thyroid cancer progression. Levels of PAK4 and PAK4 phosphorylated at serine 474 correlated significantly with tumor size and TNM stage. Furthermore, stable knockdown of PAK4 retarded cellular proliferation, migration, and invasion. Moreover, thyroid stimulating hormone-induced cellular proliferation in papillary thyroid cancer was found to be dependent on TSHR/cAMP/PKA/PAK4 signaling, with levels of phosphorylated PAK4 correlating positively with serum thyroid stimulating hormone and PKA Cα levels in patients with papillary thyroid cancer. These findings revealed a novel function of PAK4 in thyroid stimulating hormone-induced papillary thyroid cancer progression and suggest that PAK4 may become a promising diagnostic and therapeutic target for this disease.
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http://dx.doi.org/10.18632/oncotarget.15079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421896PMC
April 2017

Molecular characterisation of a DREB gene from Sophora moorcroftiana, an endemic species of plateau.

Protoplasma 2017 Jul 3;254(4):1735-1741. Epub 2017 Jan 3.

Agricultural and Animal Husbandry College, Tibet University, Nyingchi, 860000, People's Republic of China.

Various plant species in the Qinghai-Tibet Plateau exposed to harsh conditions, such as low oxygen, drought, extremely low temperatures and salinity, have evolved both molecular and physiological adaptation strategies to deal with these multiple stresses. Sophora moorcroftiana (Benth.) Baker (Fabaceae) is a highly drought-resistant endemic Sophora shrub species in the Qinghai-Tibet Plateau. In our previous study, a drought-induced DREB transcription factor gene was identified and was designated as SmDREB1. SmDREB1-GFP fusion construct was introduced into Arabidopsis protoplast to characterise the function of SmDREB1 in drought resistance. The results showed that SmDREB1 targets the nucleus of Arabidopsis protoplast. Ectopic expression of SmDREB1 in model plant species Arabidopsis was performed. The transgenic lines showed increasing expressions of drought marker genes including AtDHN, AtLEA, AtPIP2 ;2, AtPIP2;3 and AtRD29, increasing activities of antioxidant enzymes and proline contents and increasing light-use efficiency under drought stress as compared with the wild-type plants; SmDREB1 transgenic lines are more resistant to drought than wild-type plants. Therefore, the SmDREB1 is a drought-resistant transcription factor gene of S. moorcroftiana and could be a candidate in genetic engineering to improve drought resistance of plateau plant species.
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http://dx.doi.org/10.1007/s00709-016-1065-9DOI Listing
July 2017

The complete chloroplast genome of Sinopodophyllum hexandrum (Berberidaceae).

Authors:
Huie Li Qiqiang Guo

Mitochondrial DNA A DNA Mapp Seq Anal 2016 07 24;27(4):2955-6. Epub 2015 Dec 24.

a Research Institute of Tibet Plateau Ecology, Agricultural and Animal Husbandry College, Tibet University , Nyingchi , PR China.

The complete chloroplast (cp) genome of the Sinopodophyllum hexandrum (Berberidaceae) was determined in this study. The circular genome is 157,940 bp in size, and comprises a pair of inverted repeat (IR) regions of 26,077 bp each, a large single-copy (LSC) region of 86,460 bp and a small single-copy (SSC) region of 19,326 bp. The GC content of the whole cp genome was 38.5%. A total of 133 genes were identified, including 88 protein-coding genes, 37 tRNA genes and eight rRNA genes. The whole cp genome consists of 114 unique genes, and 19 genes are duplicated in the IR regions. The phylogenetic analysis revealed that S. hexandrum is closely related to Nandina domestica within the family Berberidaceae.
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http://dx.doi.org/10.3109/19401736.2015.1060458DOI Listing
July 2016

Characterization of the complete chloroplast genome of Juniperus cedrus (Cupressaceae).

Mitochondrial DNA A DNA Mapp Seq Anal 2016 11 14;27(6):4355-4356. Epub 2015 Oct 14.

a Agricultural and Animal Husbandry College, Tibet University , Nyingchi , Tibet , China.

The complete chloroplast genome of Juniperus cedrus is a circular molecule of 127 126 bp in length with 115 single copy genes and two duplicated genes (trnI-CAU and trnQ-UUG). The genome contains 82 protein-coding genes, four ribosomal RNA genes and 33 transfer RNA genes. In these genes, eight genes (rpl16, rpl2, rpoC1, petD, petB, ndhB, ndhA and atpF) harbor a single intron and two genes (rps12 and ycf3) harbor two introns. Like other sequenced chloroplast genomes of conifers, this genome does not contain canonical inverted repeats (IRs), and the overall GC content of J. cedrus chloroplast DNA is 35%. The phylogenetic analysis revealed that J. cedrus is more closely related to J. scopulorum and J. bermudiana.
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http://dx.doi.org/10.3109/19401736.2015.1089498DOI Listing
November 2016

The complete chloroplast genome of Cupressus gigantea, an endemic conifer species to Qinghai-Tibetan Plateau.

Mitochondrial DNA A DNA Mapp Seq Anal 2016 09 10;27(5):3743-4. Epub 2015 Sep 10.

a Agricultural and Animal Husbandry College, Tibet University , Nyingchi , Tibet , China .

The complete chloroplast genome of the wild Cupressus gigantea (Cupressaceae) is determined in this study. The circular genome is 128 244 bp in length with 115 single copy genes and two duplicated genes (trnI-CAU and trnQ-UUG). This genome contains 82 protein-coding genes, four ribosomal RNA genes and 31 transfer RNA genes. In these genes, eight genes (atpF, rpoC1, ndhA, ndhB, petB, petD, rpl16 and rpl2) harbor a single intron and two genes (rps12 and ycf3) harbor two introns. This genome does not contain canonical IRs, and the overall GC content is 34.7%. A maximum parsimony phylogenetic analysis revealed that C. gigantea and C. sempervirens are more closely related.
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http://dx.doi.org/10.3109/19401736.2015.1079885DOI Listing
September 2016

De novo assembly and discovery of genes that are involved in drought tolerance in Tibetan Sophora moorcroftiana.

PLoS One 2015 5;10(1):e111054. Epub 2015 Jan 5.

Agricultural and Animal Husbandry College, Tibet University, Nyingchi, Tibet, China; Key Laboratory of Forest Ecology in Tibet Plateau (Tibet University), Ministry of Education, Nyingchi, Tibet, China; National Key Station for Field Scientific Observation & Experiment, Nyingchi, Tibet, China.

Sophora moorcroftiana, a Leguminosae shrub species that is restricted to the arid and semi-arid regions of the Qinghai-Tibet Plateau, is an ecologically important foundation species and exhibits substantial drought tolerance in the Plateau. There are no functional genomics resources in public databases for understanding the molecular mechanism underlying the drought tolerance of S. moorcroftiana. Therefore, we performed a large-scale transcriptome sequencing of this species under drought stress using the Illumina sequencing technology. A total of 62,348,602 clean reads were obtained. The assembly of the clean reads resulted in 146,943 transcripts, including 66,026 unigenes. In the assembled sequences, 1534 transcription factors were identified and classified into 23 different common families, and 9040 SSR loci, from di- to hexa-nucleotides, whose repeat number is greater than five, were presented. In addition, we performed a gene expression profiling analysis upon dehydration treatment. The results indicated significant differences in the gene expression profiles among the control, mild stress and severe stress. In total, 4687, 5648 and 5735 genes were identified from the comparison of mild versus control, severe versus control and severe versus mild stress, respectively. Based on the differentially expressed genes, a Gene Ontology annotation analysis indicated many dehydration-relevant categories, including 'response to water 'stimulus' and 'response to water deprivation'. Meanwhile, the Kyoto Encyclopedia of Genes and Genomes pathway analysis uncovered some important pathways, such as 'metabolic pathways' and 'plant hormone signal transduction'. In addition, the expression patterns of 25 putative genes that are involved in drought tolerance resulting from quantitative real-time PCR were consistent with their transcript abundance changes as identified by RNA-seq. The globally sequenced genes covered a considerable proportion of the S. moorcroftiana transcriptome, and the expression results may be useful to further extend the knowledge on the drought tolerance of this plant species that survives under Plateau conditions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111054PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283959PMC
January 2016

LCH-7749944, a novel and potent p21-activated kinase 4 inhibitor, suppresses proliferation and invasion in human gastric cancer cells.

Cancer Lett 2012 Apr 13;317(1):24-32. Epub 2011 Nov 13.

Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.

P21-activated kinase 4 (PAK4), a serine/threonine protein kinase, has involved in the regulation of cytoskeletal reorganization, cell proliferation, gene transcription, oncogenic transformation and cell invasion. Moreover, PAK4 overexpression, genetic amplification and mutations were detected in a variety of human tumors, which make it potential therapeutic target. In this paper we found that LCH-7749944, a novel and potent PAK4 inhibitor, effectively suppressed the proliferation of human gastric cancer cells through downregulation of PAK4/c-Src/EGFR/cyclin D1 pathway. In addition, LCH-7749944 significantly inhibited the migration and invasion of human gastric cancer cells in conjunction with concomitant blockage of PAK4/LIMK1/cofilin and PAK4/MEK-1/ERK1/2/MMP2 pathways. Interestingly, LCH-7749944 also inhibited the formation of filopodia and induced cell elongation in SGC7901 cells. Importantly, LCH-7749944 caused successful inhibition of EGFR activity due to its inhibitory effect on PAK4. Taken together, these results provided novel insights into the development of PAK4 inhibitor and potential therapeutic strategies for gastric cancer.
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http://dx.doi.org/10.1016/j.canlet.2011.11.007DOI Listing
April 2012