MiRNA-339 targets and regulates ZNF689 to inhibit the proliferation and invasion of gastric cancer cells

Houxiang Jiang; Yinhua Liu; Kaifeng Hu; Yabin Xia; Linhu Liang; Xiaoli Zhu; Xianfeng Cheng

doi:10.21037/tcr-21-994

MiRNA-339 targets and regulates ZNF689 to inhibit the proliferation and invasion of gastric cancer cells

Transl Cancer Res. 2021 Jul;10(7):3516-3526. doi: 10.21037/tcr-21-994.

Authors

Houxiang Jiang^#¹, Yinhua Liu^#², Kaifeng Hu¹, Yabin Xia¹, Linhu Liang¹, Xiaoli Zhu¹, Xianfeng Cheng³

Affiliations

¹ Department of Gastrointestinal Surgery, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital Wannan Medical College) Wuhu, China.
² Department of Pathology, the First Affiliated Hospital of Wannan Medical College (YIjishan Hospital of Wanna Medical College), Wuhu, China.
³ Department of Laboratory Medicine, Dermatology Hospital of Chinese Academy of Medical Sciences (Institute), Nanjing, China.

^# Contributed equally.

Abstract

Background: Gastric cancer (GC) is the most common malignant tumor of the digestive system, and its mortality rate ranks first among malignant tumors. However, the pathogenesis of GC has not yet been fully elucidated. This study found that microRNA (miRNA)-339 is abnormally expressed in GC tissues. However, the role and molecular mechanism of miRNA-339 in the occurrence and development of GC are still unclear.

Methods: Fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the expression level of miRNA-339 in GC tissues and adjacent tissues and analyze the correlation with the clinicopathological characteristics of GC patients. Cell counting kit-8 (CCK-8) and Transwell experiments detected the effect of overexpression of miRNA-339 on the proliferation, invasion, and migration of GC cells. The luciferase reporter gene detected the downstream target molecules regulated by miRNA-339, and western blot was employed to detect the effect of overexpression of miRNA-339 on the expression of ZNF689.

Results: The results of fluorescence qPCR showed that miRNA-339 was less expressed in GC tissues compared with adjacent tissues, and it was correlated with the patient's clinical tumor, node, metastasis (TNM) grade and lymph node metastasis. Cell function experiments showed that overexpression of miRNA-339 can significantly inhibit the proliferation, invasion, and migration of GC cells. The luciferase reporter gene showed that miRNA-339 can bind to the 3'-UTR region of ZNF689, and overexpression of miRNA-339 can significantly inhibit the expression of ZNF689 in GC cells. Overexpression of ZNF689 can significantly block the ability of overexpression of miRNA-339 to inhibit the proliferation and migration of GC cells.

Conclusions: miRNA-339 inhibits the proliferation and invasion of GC cells through targeted regulation of the expression of ZNF689. In addition, the expression level of miRNA-339 can be used as a biomarker for the prognosis of GC.

Keywords: MicroRNA 339 (miRNA-339); ZNF689; gastric cancer (GC); invasion; proliferation.