DNA‐methylation‐mediated silencing of miR‐7‐5p promotes gastric cancer stem cell invasion via increasing Smo and Hes1

Abstract

Cancer stem cells are undifferentiated cancer cells that have self-renewal ability, a high tumorigenic activity, and a multilineage differentiation potential. MicroRNAs play a critical role in regulating gene expression during carcinogenesis. Here, we investigated the role of miR-7 and the mechanism by which it is dysregulated in gastric cancer stem cells (GCSCs). The stem cell marker, CD44, was used to sort GCSCs by fluorescence-activated cell sorting. We found that CD44 (+) cells have higher invasiveness and form more number of sphere colonies than CD44 (−) cells. Quantitative real-time polymerase chain reaction (PCR) revealed that the miR-7-5p expression was remarkably downregulated in GCSCs but was significantly increased in the methionine-deprived medium. The downregulation of miR-7-5p results from the increased DNA methylation in the promoter region using the methylation-specific PCR. Overexpression of miR-7-5p reduced the formation of colony and decreased the invasion of GCSCs through targeting Smo and Hes1 and subsequent repressing Notch and Hedgehog signaling pathways in vitro. Notably, upregulating miR-7-5p inhibited the growth of tumor in the xenograft model. Hence, these data demonstrated that miR-7-5p represses GCSC invasion through inhibition of Smo and Hes1, which provides a potential therapeutic target of gastric cancer treatment.

Nei Endonuclease VIII-Like1 (NEIL1) Inhibits Apoptosis of Human Colorectal Cancer Cells

“…Moreover, it has been shown that miR-7 is associated with the progression of various tumors, including gastric cancer, lung cancer, breast cancer, and glioma [11]. DNA methylation-mediated miR-7-5p silencing would promote the gastric cancer stem cell invasion by increasing Smo and Hes1 [12]. Furthermore, methylation of miR-7 can be used as a biomarker for predicting the poor survival in patients with non-small cell lung cancer at the early stage.…”

Hypermethylation of the PZP gene is associated with hepatocellular carcinoma cell proliferation, invasion and migration

“…A number of research studies have unveiled that aberrant DNA Abbreviations 5-aza-dC, 5-aza-2ʹ-deoxycytidine; CGI, CpG island; DEmRNA, differentially expressed mRNA; FC, fold change; HCC, hepatocellular carcinoma; MSP, methylation-specific PCR; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide; NC, negative control; PZP, pregnancy zone protein; SD, standard deviation; TCGA-LIHC, The Cancer Genome Atlas Liver Hepatocellular Carcinoma. methylation is able to facilitate tumor cell proliferation, invasion and migration of colorectal cancer [8], gastric cancer [9], liver cancer [10,11], HCC [12] and so on.…”

Down-Regulation of miR-7 in Gastric Cancer Is Associated With Elevated LDH-A Expression and Chemoresistance to Cisplatin

“…miR-7 has been found in recent years to serve as a tumor suppressor in several tumor types, but its role in GC has not previously been demonstrated. Recent reports showed that miR-7 plays a certain role in gastric cancer and can be regulated by Circular RNA, long non-coding RNA or DNA methylation (Pan et al, 2018;Yang et al, 2018;Xin et al, 2020). Herein, we found miR-7 to be expressed at lower levels in GC tumors, and when overexpressed miR-7 inhibited the proliferation and glycolytic metabolism of GC cells, in addition to increasing their cisplatin sensitivity.…”