MicroRNA-543 controls pancreatic cancer development by LINC00847-microRNA-543-STK31 axis

Yan Liu; Jun Wei; Chao Wang; Zihui Meng; Duqiang Luo; Xiaoling Zhao; Ruizhi Hou

doi:10.21037/jgo-22-1017

MicroRNA-543 controls pancreatic cancer development by LINC00847-microRNA-543-STK31 axis

J Gastrointest Oncol. 2022 Dec;13(6):3263-3277. doi: 10.21037/jgo-22-1017.

Authors

Yan Liu¹, Jun Wei², Chao Wang³, Zihui Meng⁴, Duqiang Luo⁵, Xiaoling Zhao⁵, Ruizhi Hou⁶

Affiliations

¹ Department of Gastrointestinal and Colonretal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
² Department of Clinical Research, China-Japan Union Hospital of Jilin University, Changchun, China.
³ Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
⁴ Department of Hepatic Biliary Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
⁵ College of Life Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding, China.
⁶ Department of Ultrasonography, China-Japan Union Hospital of Jilin University, Changchun, China.

Abstract

Background: Pancreatic cancer (PC) is one of the most malignant cancers of the gastrointestinal tract. However, the study of targeted therapy research in PC is not very thorough. Therefore, targeted molecular markers are needed to aid in the diagnosis and treatment of PC.

Methods: In our research, we investigated the biological functions and molecular mechanism of microRNA-543 in PC. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to analyze the transcription and protein expression of microRNA-543, Serine/threonine kinase 31 (STK31), and LINC00847 in BxPC-3 and PANC-1 cells. Subsequently, Cell Counting Kit-8 (CCK-8), Transwell, colony formation, and flow cytometry (FCM) assays were utilized to evaluate cell growth, migration, invasion, and apoptosis. WB and fluorescence in-situ hybridization (FISH) were used to evaluate the epithelial-mesenchymal transition (EMT) process and subcellular localization. RNA immunoprecipitation (RIP), double luciferase reporter, and RNA-pull down assays were performed to determine the targeting relationship between microRNA-543 and STK31 or microRNA-543 and LINC00847.

Results: While microRNA-543 expression was discovered to be low in PC, LINC00847 and STK31 were overexpressed at significant levels. MicroRNA-543 knockdown dramatically increased PC cell growth, invasion, metastasis, and EMT, as well as decreased apoptosis in functional studies. Furthermore, microRNA-543 and STK31 were found to be mutual targets. LINC00847 acted as a molecular sponge for microRNA-543 and a competitive endogenous RNA (ceRNA) for STK31, thereby increasing STK-31 transcription.

Conclusions: Our results suggest that microRNA-543, through the LINC00847/microRNA-543/STK31 axis, plays a role in the development of PC as a tumor suppressor. As a result, microRNA-543 may prove to be an effective diagnostic and therapeutic target for PC.

Keywords: LINC00847; Pancreatic cancer (PC); biological function; epithelial–mesenchymal transition (EMT); microRNA-543.