Functional Effects of let-7g Expression in Colon Cancer Metastasis.

Che-Mai Chang,Ben-Kuen Chen,Yu-Jui Wan,Chien-Yu Huang,Siou-Jin Chiu,Wei-Chiao Chang,Yao-Ting Tsai,Jaw-Yuan Wang,Zhi-Feng Maio,Henry Wong,Wen-Li Hsu

doi:10.3390/cancers11040489

Abstract

MicroRNA regulation is crucial for gene expression and cell functions. It has been linked to tumorigenesis, development and metastasis in colorectal cancer (CRC). Recently, the let-7 family has been identified as a tumor suppressor in different types of cancers. However, the function of the let-7 family in CRC metastasis has not been fully investigated. Here, we focused on analyzing the role of let-7g in CRC. The Cancer Genome Atlas (TCGA) genomic datasets of CRC and detailed data from a Taiwanese CRC cohort were applied to study the expression pattern of let-7g. In addition, in vitro as well as in vivo studies have been performed to uncover the effects of let-7g on CRC. We found that the expression of let-7g was significantly lower in CRC specimens. Our results further supported the inhibitory effects of let-7g on CRC cell migration, invasion and extracellular calcium influx through store-operated calcium channels. We report a critical role for let-7g in the pathogenesis of CRC and suggest let-7g as a potential therapeutic target for CRC treatment.

Highlights

MicroRNAs are short, single-stranded non-coding RNAs which function as post-transcriptional regulators of gene expression and are involved in fundamental biological processes
The numbers of migrating and invasive cells significantly decreased with let-7g overexpression and SKF96365 treatment (Figure 4B,C). These results suggest that let-7g and the Store-Operated Calcium (SOC) inhibitor had similar inhibitory effects on colorectal cancer (CRC) cell migration and invasion
We further examined the influences of let-7g and the SOC inhibitor on the epithelial-mesenchymal transition (EMT), which was indicated to be involved in the progression and metastasis of CRC

Summary

Introduction

Micro (mi)RNAs are short, single-stranded non-coding RNAs which function as post-transcriptional regulators of gene expression and are involved in fundamental biological processes. Many studies have been published showing that miRNAs are involved in critical human diseases, including cancer [2,3,4]. MiRNAs suppress gene expression through imperfect base-pairing with a complementary sequence in the 30 -untranslated region (UTR) of target messenger (m)RNAs and inhibit target protein synthesis by preventing translation or inducing mRNA degradation [5,6]. The biological roles of miRNAs are as regulators of several cellular events, such as proliferation, differentiation and apoptosis, which are associated with cancer progression [6,7]. MiR-21 mediates the post-transcriptional modification of a tumor suppressor, thereby stimulating colorectal cancer (CRC) invasion, intravasation and metastasis [8]. Ma et al stated that miR-9 causes E-cadherin downregulation and activates β-catenin signaling to enhance the level of vascular endothelial growth factor (VEGF), which in turn promotes breast tumor angiogenesis [9]

Methods

Discussion

Conclusion