Upregulated MiRNA-543 Promotes the Proliferation and Migration of Gastric Carcinoma by Downregulating KLF6

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2020 Oct 12

PMID 33042458

Authors

Qiong Wang

Lihua Mu

Hongqing Xi

Chunyan Zhang

Jing Yuan

Min Zhu

Mingyang Li

Affiliations

Soon will be listed here.

Abstract

This study aims to uncover the potential function of MicroRNA-543 (miRNA-543) in the pathogenesis of gastric carcinoma and the possible mechanism. MiRNA-543 levels in gastric carcinoma tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Regulatory effects of miRNA-543 on proliferative and migratory abilities of AGS and MKN45 cells were assessed. The downstream target of miRNA-543 was predicted by online bioinformatics and verified by dual-luciferase reporter gene assay. At last, rescue experiments were carried out to uncover the interaction between miRNA-543 and Krüppel-like factor 6 (KLF6) in the progression of gastric carcinoma. MiRNA-543 was upregulated in gastric carcinoma tissues and cell lines. Particularly, gastric carcinoma patients with advanced stage or positive metastasis expressed higher abundance of miRNA-543. Overexpression of miRNA-543 promoted proliferative ability in gastric carcinoma, manifesting as increased viability, EdU-positive ratio and migratory cell number in AGS and MKN45 cells. KLF6 was proved to be the downstream target of miRNA-543. Both mRNA and protein levels of KLF6 were negatively regulated by miRNA-543 in gastric carcinoma cells. Silence of KLF6 was able to reverse the regulatory effects of miRNA-543 inhibitor on proliferative and migratory abilities in gastric carcinoma. MiRNA-543 is highly expressed in gastric carcinoma. It accelerates gastric carcinoma cells to proliferate and migrate by negatively regulating KLF6 level.

References

Liou J, Lee Y, El-Omar E, Wu M . Efficacy and Long-Term Safety of Eradication for Gastric Cancer Prevention. Cancers (Basel). 2019; 11(5). PMC: 6562927. DOI: 10.3390/cancers11050593. View

Narla G, Kremer-Tal S, Matsumoto N, Zhao X, Yao S, Kelley K . In vivo regulation of p21 by the Kruppel-like factor 6 tumor-suppressor gene in mouse liver and human hepatocellular carcinoma. Oncogene. 2007; 26(30):4428-34. DOI: 10.1038/sj.onc.1210223. View

Lang U, Kocabayoglu P, Cheng G, Ghiassi-Nejad Z, Munoz U, Vetter D . GSK3β phosphorylation of the KLF6 tumor suppressor promotes its transactivation of p21. Oncogene. 2012; 32(38):4557-64. PMC: 3892988. DOI: 10.1038/onc.2012.457. View

Coutzac C, Pernot S, Chaput N, Zaanan A . Immunotherapy in advanced gastric cancer, is it the future?. Crit Rev Oncol Hematol. 2019; 133:25-32. DOI: 10.1016/j.critrevonc.2018.10.007. View

Li W, Cui Y, Wang D, Wang Y, Wang L . MiR-141-3p functions as a tumor suppressor through directly targeting ZFR in non-small cell lung cancer. Biochem Biophys Res Commun. 2019; 509(3):647-656. DOI: 10.1016/j.bbrc.2018.12.089. View

Bai S, Ji R, Wei H, Guo Q, Yuan H, Chen Z . Serum miR-551b-3p is a potential diagnostic biomarker for gastric cancer. Turk J Gastroenterol. 2019; 30(5):415-419. PMC: 6505657. DOI: 10.5152/tjg.2019.17875. View

Wang F . miR-384 targets metadherin gene to suppress growth, migration, and invasion of gastric cancer cells. J Int Med Res. 2019; 47(2):926-935. PMC: 6381512. DOI: 10.1177/0300060518817171. View

Sampson V, Yoo S, Kumar A, Vetter N, Kolb E . MicroRNAs and Potential Targets in Osteosarcoma: Review. Front Pediatr. 2015; 3:69. PMC: 4547013. DOI: 10.3389/fped.2015.00069. View

Liu F, Di Wang X . miR-150-5p represses TP53 tumor suppressor gene to promote proliferation of colon adenocarcinoma. Sci Rep. 2019; 9(1):6740. PMC: 6494853. DOI: 10.1038/s41598-019-43231-5. View

10.

Zhang H, Guo X, Feng X, Wang T, Hu Z, Que X . MiRNA-543 promotes osteosarcoma cell proliferation and glycolysis by partially suppressing PRMT9 and stabilizing HIF-1α protein. Oncotarget. 2016; 8(2):2342-2355. PMC: 5356804. DOI: 10.18632/oncotarget.13672. View

11.

Zhao H, Diao C, Wang X, Xie Y, Liu Y, Gao X . MiR-543 Promotes Migration, Invasion and Epithelial-Mesenchymal Transition of Esophageal Cancer Cells by Targeting Phospholipase A2 Group IVA. Cell Physiol Biochem. 2018; 48(4):1595-1604. DOI: 10.1159/000492281. View

12.

Ye T, Yang M, Huang D, Wang X, Xue B, Tian N . MicroRNA-7 as a potential therapeutic target for aberrant NF-κB-driven distant metastasis of gastric cancer. J Exp Clin Cancer Res. 2019; 38(1):55. PMC: 6364399. DOI: 10.1186/s13046-019-1074-6. View

13.

Hosoda K, Watanabe M, Yamashita K . Re-emerging role of macroscopic appearance in treatment strategy for gastric cancer. Ann Gastroenterol Surg. 2019; 3(2):122-129. PMC: 6422795. DOI: 10.1002/ags3.12218. View

14.

Guo H, Ji F, Zhao X, Yang X, He J, Huang L . MicroRNA-371a-3p promotes progression of gastric cancer by targeting TOB1. Cancer Lett. 2018; 443:179-188. DOI: 10.1016/j.canlet.2018.11.021. View

15.

Zan Y, Wang B, Liang L, Deng Y, Tian T, Dai Z . MicroRNA-139 inhibits hepatocellular carcinoma cell growth through down-regulating karyopherin alpha 2. J Exp Clin Cancer Res. 2019; 38(1):182. PMC: 6498602. DOI: 10.1186/s13046-019-1175-2. View

16.

Necula L, Matei L, Dragu D, Neagu A, Mambet C, Nedeianu S . Recent advances in gastric cancer early diagnosis. World J Gastroenterol. 2019; 25(17):2029-2044. PMC: 6506585. DOI: 10.3748/wjg.v25.i17.2029. View

17.

Huang X, Tang F, Weng Z, Zhou M, Zhang Q . MiR-591 functions as tumor suppressor in breast cancer by targeting TCF4 and inhibits Hippo-YAP/TAZ signaling pathway. Cancer Cell Int. 2019; 19:108. PMC: 6480894. DOI: 10.1186/s12935-019-0818-x. View

18.

Lei Z, Ma X, Li H, Zhang Y, Gao Y, Fan Y . Up-regulation of miR-181a in clear cell renal cell carcinoma is associated with lower KLF6 expression, enhanced cell proliferation, accelerated cell cycle transition, and diminished apoptosis. Urol Oncol. 2017; 36(3):93.e23-93.e37. DOI: 10.1016/j.urolonc.2017.09.019. View

19.

Parvaee P, Sarmadian H, Khansarinejad B, Amini M, Mondanizadeh M . Plasma Level of MicroRNAs, MiR-107, MiR-194 and MiR-210 as Potential Biomarkers for Diagnosis Intestinal-Type Gastric Cancer in Human. Asian Pac J Cancer Prev. 2019; 20(5):1421-1426. PMC: 6857871. DOI: 10.31557/APJCP.2019.20.5.1421. View

20.

Ke N, Pi L, Liu Q, Chen L . Long noncoding RNA SNHG7 inhibits high glucose-induced human retinal endothelial cells angiogenesis by regulating miR-543/SIRT1 axis. Biochem Biophys Res Commun. 2019; 514(2):503-509. DOI: 10.1016/j.bbrc.2019.04.141. View