LncRNA MAFG-AS1 regulates miR-125b-5p/SphK1 axis to promote the proliferation, migration, and invasion of bladder cancer cells

Chenye Tang,Xiao Wang,Kean Chen,Zhiling Tang,Xiao Guo,Yuntao Wu

doi:10.1007/s13577-020-00470-3

Abstract

MAFG-AS1 is an oncogenic lncRNA in multiple types of cancer. However, its role in bladder cancer (BC) remains unclear. The present study aimed to investigate the function of MAFG-AS1 in BC. BC and paired non-tumor tissues were collected. Two BC cell lines HT01197 and HT-1376 were used. Dual luciferase activity assay, RT-qPCR, western blot, CCK-8, transwell invasion assay, and wound healing assay were performed. We found that MAFG-AS1 was significantly up-regulated in BC tissues and predicted a poor survival rate. MAFG-AS1 interacted with miR-125b-5p. However, the expression levels of MAFG‑AS1 and miR-125b-5p were not obviously correlated in BC tissues, and MAFG‑AS1 and miR-125b-5p did not regulate the expression of each other. Interestingly, we found that SphK1, a downstream target of miR-125b-5p, was negatively correlated with miR-125b-5p, while it was positively correlated with MAFG-AS1 across BC tissues. In addition, overexpression of MAFG‑AS1 upregulated the expression of SphK1 in BC cells, and attenuated the inhibitory effects of miR-125b-5p on the expression of SphK1. Functional assays showed that overexpression of MAFG‑AS1 promoted BC cell proliferation, migration, and invasion, while its effects were attenuated by overexpression of miR-125b-5p. Moreover, overexpression of miR-125b-5p inhibited BC cell proliferation, migration, and invasion, while its effects were alleviated by overexpression of SphK1. Taken together, our findings demonstrated that MAFG-AS1 has an oncogenic role in BC by regulating the miR-125b-5p/SphK1 axis. MAFG-AS1 might serve as a good diagnostic marker and a potential therapeutic target of BC.

Highlights

Bladder cancer (BC) affected 549,393 new cases, accounting for 3.0% of all new cancer cases, and caused 199,922 deaths, accounting for 2.1% of all cancer deaths in 2018 worldwide [1]
Dual luciferase activity assay was performed by co-transfecting MAFG-AS1 vector + miR125b-5p or MAFG-AS1 vector + negative control (NC) miRNA (NC miRNA group) into HT-1197 cells
We found that Sphingosine kinase 1 (SphK1) was negatively correlated with miR-125b-5p, while it was positively correlated with MAFG-AS1 across BC tissues

Summary

Introduction

Bladder cancer (BC) affected 549,393 new cases, accounting for 3.0% of all new cancer cases, and caused 199,922 deaths, accounting for 2.1% of all cancer deaths in 2018 worldwide [1]. The high mortality rate of BC is mainly caused by the existence of tumor metastasis in a considerable portion of Chenye Tang, Yuntao Wu contributed to this work. The main risk factor of BC is the exposure to carcinogens, such as tobacco, which can induce BC by hypermethylation and DNA damage [4, 5]. Exposure to carcinogens is not sufficient for the occurrence and development of BC. Genetic alterations, such as germline mutations or epigenetic modification, independent from carcinogen, contribute to the occurrence of BC [6]

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