|Table of Contents|

Mechanism of miR-140-5p targeting HDAC7 inhibiting proliferation,migration and invasion of non-small cell lung cancer cells

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

Issue:
2023 03
Page:
417-422
Research Field:
Publishing date:

Info

Title:
Mechanism of miR-140-5p targeting HDAC7 inhibiting proliferation,migration and invasion of non-small cell lung cancer cells
Author(s):
ZHANG Jing1; MENG Wei1; ZHAO Lixia1; LI Chen2; SHI Jing1; ZHAI Minghui1; FANG Yuan1; LI Peng1
1.Department of Oncology;2.Department of Respiratory and Critical Care Medicine,First Affiliated Hospital of Hebei North University，Hebei Zhangjiakou 075000，China.
Keywords:
non-small cell lung cancer; miR-140-5p; proliferation; migration; invasion; mechanism study
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2023.03.005
Abstract:
Objective:To explore the mechanism of miR-140-5p targeting HDAC7 regulating proliferation,migration and invasion of non-small cell lung cancer cells.Methods:The expression level of miR-140-5p in human NSCLC tissues and adjacent tissues was detected by qRT-PCR.A549 cells were transfected with miR-140-5p mimic（mimic) and miR-140-5p NC（negative control).Cell proliferation was detected by CCK8 assay and colony formation assay.Cell migration and invasion were detected by scratch test and Transwell test.The double luciferase target experiment verified the targeting relationship between miR-140-5p and HDAC7.Western blot was used to detect the expression levels of HDAC7,PI3K,p-PI3K,AKT and p-AKT.Results:The expression level of miR-140-5p in NSCLC tissues was significantly lower than that in adjacent tissues（P<0.01).Compared with miR-140-5p NC group,the proliferation ability of A549 cells at 48 and 72 h after overexpression of miR-140-5p significantly decreased（P<0.05),the ability of cell clone formation,cell migration and invasion were decreased（all P<0.05),and the protein levels of p-PI3K and p-AKT in PI3K/AKT signaling pathway were significantly decreased（all P<0.05).Bioinformatics predicted that HDAC7 might be a target gene of miR-140-5p,and the results of double luciferase assay confirmed that miR-140-5p could directly target the expression of HDAC7.Conclusion:miR-140-5p inhibits the proliferation,migration and invasion of NSCLC A549 cells by targeting HDAC7 expression,which may be related to the inhibition of PI3K/AKT signaling pathway.

References:

[1]IMYANITOV EN,IYEVLEVA AG,LEVCHENKO EV.Molecular testing and targeted therapy for non-small cell lung cancer:Current status and perspectives［J］.Crit Rev Oncol Hematol,2021,157:103194.
[2]SANKAR K,GADGEEL SM,QIN A.Molecular therapeutic targets in non-small cell lung cancer［J］.Expert Rev Anticancer Ther,2020,20(8):647-661.
[3]KONG F,WANG Z,LIAO D,et al.Non-small cell lung cancer:Challenge and improvement of immune drug resistance［J］.Front Oncol,2021,11:739191.
[4]JONNA S,SUBRAMANIAM DS.Molecular diagnostics and targeted therapies in non-small cell lung cancer（NSCLC):an update［J］.Discov Med,2019,27(148):167-170.
[5]AHN YH,KO YH.Diagnostic and therapeutic implications of microRNAs in non-small cell lung cancer［J］.Int J Mol Sci,2020,21(22):8782.
[6]ZHONG S,GOLPON H,ZARDO P,et al.miRNAs in lung cancer.A systematic review identifies predictive and prognostic miRNA candidates for precision medicine in lung cancer［J］.Transl Res,2021,230:164-196.
[7]EBRAHIMI SO,REIISI S,SHAREEF S.miRNAs,oxidative stress,and cancer:A comprehensive and updated review［J］.J Cell Physiol,2020,235(11):8812-8825.
[8]YU B,YOU W,CHEN G,et al.MiR-140-5p inhibits cell proliferation and metastasis by regulating MUC1 via BCL2A1/MAPK pathway in triple negative breast cancer［J］.Cell Cycle,2019,18(20):2641-2650.
[9]FANG Z,YIN S,SUN R,et al.miR-140-5p suppresses the proliferation,migration and invasion of gastric cancer by regulating YES1［J］.Mol Cancer,2017,16(1):139.
[10]TANG YH,HE GL,HUANG SZ,et al.The long noncoding RNA AK002107 negatively modulates miR-140-5p and targets TGFBR1 to induce epithelial-mesenchymal transition in hepatocellular carcinoma［J］.Mol Oncol,2019,13(5):1296-1310.
[11]CASLINI C,HONG S,BAN YJ,et al.HDAC7 regulates histone 3 lysine 27 acetylation and transcriptional activity at super-enhancer-associated genes in breast cancer stem cells［J］.Oncogene,2019,38(39):6599-6614.
[12]ZHU T,BAO X,CHEN M,et al.Mechanisms and future of non-small cell lung cancer metastasis［J］.Front Oncol,2020,10:585284.
[13]SUSTER DI,MINO-KENUDSON M.Molecular pathology of primary non-small cell lung cancer［J］.Arch Med Res,2020,51(8):784-798.
[14]YANG P,XIONG J,ZUO L,et al.miR-140-5p regulates cell migration and invasion of non-small cell lung cancer cells through targeting VEGFA［J］.Mol Med Rep,2018,18(3):2866-2872.
[15]ZHOU W,WANG X,YIN D,et al.Effect of miR-140-5p on the regulation of proliferation and apoptosis in NSCLC and its underlying mechanism［J］.Exp Ther Med,2019,18(2):1350-1356.
[16]LI Q,YAO Y,EADES G,et al.Downregulation of miR-140 promotes cancer stem cell formation in basal-like early stage breast cancer［J］.Oncogene,2014,33(20):2589-2600.
[17]GAO S,LIU H,HOU S,et al.MiR-489 suppresses tumor growth and invasion by targeting HDAC7 in colorectal cancer［J］.Clin Transl Oncol,2018,20(6):703-712.
[18]CUTANO V,DI GIORGIO E,MINISINI M,et al.HDAC7-mediated control of tumour microenvironment maintains proliferative and stemness competence of human mammary epithelial cells［J］.Mol Oncol,2019,13(8):1651-1668.
[19]YU X,WANG M,WU J,et al.ZNF326 promotes malignant phenotype of glioma by up-regulating HDAC7 expression and activating Wnt pathway［J］.J Exp Clin Cancer Res,2019,38(1):40.
[20]SANG Y,SUN L,WU Y,et al.Histone deacetylase 7 inhibits plakoglobin expression to promote lung cancer cell growth and metastasis［J］.Int J Oncol,2019,54(3):1112-1122.
[21]PEIXOTO P,BLOMME A,COSTANZA B,et al.HDAC7 inhibition resets STAT3 tumorigenic activity in human glioblastoma independently of EGFR and PTEN:new opportunities for selected targeted therapies［J］.Oncogene,2016,35(34):4481-4494.
[22]YU Y,CAO F,YU X,et al.The expression of HDAC7 in cancerous gastric tissues is positively associated with distant metastasis and poor patient prognosis［J］.Clin Transl Oncol,2017,19(8):1045-1054.
[23]LIM HJ,CROWE P,YANG JL.Current clinical regulation of PI3K/PTEN/Akt/mTOR signalling in treatment of human cancer［J］.J Cancer Res Clin Oncol,2015,141(4):671-689.

Memo

Memo:
河北省科技支撑计划（编号：20377717D）；河北省张家口市科技局指导性项目（编号：2021047D）
Last Update: 2022-12-30