MiR-142-3p Modulates Cell Invasion and Migration via PKM2-Mediated Aerobic Glycolysis in Colorectal Cancer

JunYu Ren,Guoqing Pan,Wenliang Li,Jun Yang,Hongbin Zhang,Ruize Zhou,Fengchang Huang,Ning Xu,Elena Andreucci

doi:10.1155/2021/9927720

JunYu Ren, Guoqing Pan + Show 7 more

Open Access

https://doi.org/10.1155/2021/9927720

Copy DOI

Abstract

Decreased expression of miR-142-3p was observed in human cancers. However, the function and mechanism of miR-142-3p in human colorectal cancer remain obscure. The expressions of miR-142-3p in human colorectal cancer tissues and cell lines were measured by RT-qPCR. The effects of miR-142-3p on cell invasion and migration were detected by transwell assays. The efficiency of aerobic glycolysis was determined by glucose consumption and lactate production. Dual-luciferase reporter assays were performed to confirm the correlation between miR-142-3p and pyruvate kinase isozyme M2 (PKM2). The level of PKM2 was assessed by western blotting. Our results showed that the expression of miR-142-3p was decreased both in human colorectal cancer tissues and in cells. Overexpression of miR-142-3p in cell line attenuated colorectal cancer cell invasion and migration. About the underlying mechanism, we found that miR-142-3p modulated aerobic glycolysis via targeting pyruvate kinase M2 (PKM2). In addition, we demonstrated PKM2 and PKM2-mediated aerobic glycolysis contributes to miR-142-3p-mediated colorectal cancer cell invasion and migration. Hence, these data suggested that miR-142-3p was a potential therapeutic target for the treatment of human colorectal cancer.

Highlights

Colorectal cancer (CRC) is a common neoplasm with an increased rate of morbidity and mortality, and it has become a predominant malignancy worldwide [1]
Accumulating evidence demonstrated that the modulation of aerobic glycolysis by miRNA was achieved by targeting glycolysis-related enzymes including phosphofructokinase-1 (PFK1) [14], pyruvate dehydrogenase kinase 1 (PDK1) [15], hexokinase 2 (HK2) [13], and pyruvate kinase M2 (PKM2) [16]
The results showed that overexpression of PKM2 resulted in increased cellular glucose uptake and lactate production, which suggested that overexpression of PKM2 in colorectal cancer cells enhanced aerobic glycolysis (Figures 3(c) and 3(d))

Summary

Introduction

Colorectal cancer (CRC) is a common neoplasm with an increased rate of morbidity and mortality, and it has become a predominant malignancy worldwide [1]. Studies indicated that aerobic glycolysis was involved in cancer cell aggressive behavior [11, 12]. Accumulating evidence demonstrated that the modulation of aerobic glycolysis by miRNA was achieved by targeting glycolysis-related enzymes including phosphofructokinase-1 (PFK1) [14], pyruvate dehydrogenase kinase 1 (PDK1) [15], hexokinase 2 (HK2) [13], and pyruvate kinase M2 (PKM2) [16]. It has been well characterized that PKM2 plays a significant role in cancer development via aerobic glycolysis [17]. We showed that miR-142-3p was negative related to colorectal cancer cell invasion and migration. PKM2 and PKM2regulated aerobic glycolysis were required for miR-142-3pmediated cancer progression. All of these results indicated that miR-142-3p modulates cell invasion and migration via mediating aerobic glycolysis in colorectal cancer

Materials and Methods

Results

Discussion