|Table of Contents|

Effect of miR-151a-5p on proliferation and metastasis of colorectal cancer cells and its mechanism

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 17
Page:
3139-3144
Research Field:
Publishing date:

Info

Title:
Effect of miR-151a-5p on proliferation and metastasis of colorectal cancer cells and its mechanism
Author(s):
LIU Xianju1; XIE Yaya1; CAO Lijun1; MA Tiantian2; YANG Caina2; ZHANG Xingxing3; CHEN Jinlian3
1.School of Medicine,Anhui University of Science and Technology,Anhui Huainan 232000,China;2.Jinzhou Medical University,Liaoning Jinzhou 121001,China;3.Department of Gastroenterology,the Sixth People's Hospital(South Campus),Affiliated to Shanghai Jiao Tong University,Shanghai 201499,China.
Keywords:
miR-151a-5p; colorectal cancer; epithelial-mesenchymal transition; TGF-β/Smad signaling pathway
PACS:
R735.3
DOI:
10.3969/j.issn.1672-4992.2023.17.001
Abstract:
Objective：To investigate the biological function and mechanism of miR-151a-5p in colorectal cancer(CRC) cells.Methods:The expression of miR-151a-5p in colorectal cancer cells was tested by qRT-PCR，and miR-151a-5p mimics/inhibitor small interfering and control oligonucleotides were transfected into HCT116 and SW480 cells respectively.The biological function of over-expressed and knockdown miR-151a-5p on CRC cells were verified by CCK-8,cell colony formation,Transwell invasion and migration experiment and Western blot experiment.Results:The results of qRT-PCR were showed that the expression level of miR-151a-5p was lower in HCT116 cells and higher in SW480 cells.CCK-8 assay and clonal formation assay showed that compared with the control group,the proliferation ability of HCT116 cells increased significantly after overexpression of miR-151a-5p,which the result of SW480 cells knocking down miR-151a-5p were opposite.Transwell assay showed that compared with the corresponding control group,the ability of cell migration and invasion in HCT116-mimics group was enhanced.However,the ability of cell migration and invasion decreased in SW480-inhibitor group.Western blot results showed that the protein expression levels of E-cadherin and ZO-1 were reduced and the expression levels of N-cadherin,Vimentin,β-Catenin,MMP2,MMP9 protein and TGF-β/Smad signaling pathway related protein were increased in the HCT116-mimics group compared to the control group,while the opposite result was observed in the SW480-inhibitor group.Conclusion:miR-151a-5p promotes the proliferation,migration,and invasion of CRC cells,and the mechanism may be related to the promotion of EMT process.The change of TGF-β/Smad signaling pathway protein during EMT suggests that TGF-β/Smad signaling pathway may be involved in regulating this phenotype.

References:

［1］SIEGEL RL,MILLER KD,WAGLE NS,et al.Cancer statistics,2023［J］.CA Cancer J Clin,2023,73:17-48.
［2］XI Y,XU P.Global colorectal cancer burden in 2020 and projections to 2040［J］.Transl Oncol,2021,14(10):101174.
［3］ALI SYEDA Z,LANGDEN SSS,MUNKHZUL C,et al.Regulatory mechanism of microRNA expression in cancer［J］.Int J Mol Sci,2020,21(5)：1723.
［4］KUIPERS EJ,GRADY WM,LIEBERMAN D,et al.Colorectal cancer［J］.Nat Rev Dis Primers,2015,1:15065.
［5］WANG H.MicroRNAs and apoptosis in colorectal cancer［J］.Int J Mol Sci,2020,21(15)：5353.
［6］ROSKOSKI R.Small molecule inhibitors targeting the EGFR/ErbB family of protein-tyrosine kinases in human cancers［J］.Pharmacol Res,2019,139:395-411.
［7］XIE YH,CHEN YX,FANG JY.Comprehensive review of targeted therapy for colorectal cancer［J］.Signal Transduct Target Ther,2020,5(1):22.
［8］MISHRA S,YADAV T,RANI V.Exploring miRNA based approaches in cancer diagnostics and therapeutics［J］.Crit Rev Oncol Hematol,2016,98:12-23.
［9］GUO S,ZHANG J,ZHAO YY,et al.The expressions of miR-151a-5p and miR-23b in lung cancer tissues and their effects on the biological functions of lung cancer A549 cells［J］.Eur Rev Med Pharmacol Sci,2020,24(12):6779-6785.
［10］HU H,JIANG L,KANG X,et al.Extracellular vesicles derived from lung cancer cells promote the progression of lung cancer by delivering miR-151a-5p［J］.Exp Cell Res,2023,425(1):113526.
［11］FAN X,CAO M,LIU C,et al.Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer［J］.Cancer Biomark,2021,31(2):127-138.
［12］ZHANG H,ZHU M,SHAN X,et al.A panel of seven-miRNA signature in plasma as potential biomarker for colorectal cancer diagnosis［J］.Gene,2019,687:246-254.
［13］NANTAJIT D,LIN D,LI JJ.The network of epithelial-mesenchymal transition:potential new targets for tumor resistance［J］.J Cancer Res Clin Oncol,2015,141(10):1697-1713.
［14］DONGRE A,WEINBERG RA.New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer［J］.Nat Rev Mol Cell Biol,2019,20(2):69-84.
［15］KHRI VM,SAARIALHO-KERE U.Matrix metalloproteinases and their inhibitors in tumour growth and invasion［J］.Ann Med,1999,31(1):34-45.
［16］ABDEL-HAMID NM,ABASS SA.Matrix metalloproteinase contribution in management of cancer proliferation,metastasis and drug targeting［J］.Mol Biol Rep,2021,48(9):6525-6538.
［17］LEE JH,MASSAGU J.TGF-β in developmental and fibrogenic EMTs［J］.Semin Cancer Biol,2022,86(Pt 2):136-145.
［18］ZHANG Y,CAO L,XIE Y,et al.Agmatinase facilitates the tumorigenesis of pancreatic adenocarcinoma through the TGFβ/Smad pathway［J］.Exp Ther Med,2022,24(2):490.
［19］SAITOH M.Epithelial-mesenchymal transition is regulated at post-transcriptional levels by transforming growth factor-β signaling during tumor progression［J］.Cancer Sci,2015,106(5):481-488.
［20］BRENNECKE J,COHEN SM.Towards a complete description of the microRNA complement of animal genomes［J］.Genome Biol,2003,4(9):228.
［21］CASTAO C,KALKO S,NOVIALS A,et al.Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice［J］.Proc Natl Acad Sci USA,2018,115(48):12158-12163.
［22］IORIO MV,VISONE R,DI LEVA G,et al.MicroRNA signatures in human ovarian cancer［J］.Cancer Res,2007,67(18):8699-8707.
［23］SELVAMANI A,SATHYAN P,MIRANDA RC,et al.An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model［J］.PLoS One,2012,7(2):e32662.
［24］QADIR MI,FAHEEM A.miRNA:A diagnostic and therapeutic tool for pancreatic cancer［J］.Crit Rev Eukaryot Gene Expr,2017,27(3):197-204.
［25］KABZINSKI J,MACZYNSKA M,MAJSTEREK I.MicroRNA as a novel biomarker in the diagnosis of head and neck cancer［J］.Biomolecules,2021,11(6)：844.
［26］DE SIMONE V,FRANZ E,RONCHETTI G,et al.Th17-type cytokines,IL-6 and TNF-α synergistically activate STAT3 and NF-κB to promote colorectal cancer cell growth［J］.Oncogene,2015,34(27):3493-3503.
［27］GENG L,CHAUDHURI A,TALMON G,et al.MicroRNA-192 suppresses liver metastasis of colon cancer［J］.Oncogene,2014,33(46):5332-5340.
［28］CHEN DL,LU YX,ZHANG JX,et al.Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression［J］.Theranostics,2017,7(19):4836-4849.
［29］ZHANG X,MA X,AN H,et al.Upregulation of microRNA-125b by G-CSF promotes metastasis in colorectal cancer［J］.Oncotarget,2017,8(31):50642-50654.

Memo

Memo:
上海市卫生健康委员会青年科研基金（编号：20204Y0181）；上海市奉贤区（社会类）科技发展基金（编号：20211805）
Last Update: 2023-07-31