Dataset Information

MiR-148a Regulates the Stem Cell-Like Side Populations Distribution by Affecting the Expression of ACVR1 in Esophageal Squamous Cell Carcinoma.

ABSTRACT: Introduction:Esophageal squamous cell carcinoma (ESCC) is a malignant tumor disease with high mortality and morbidity rates, especially for a terminal cancer. At present, the prognosis and treatment of ESCC cannot effectively control or inhibit the spread and proliferation of tumor cells. microRNAs, a class of small spliced RNAs, are essential in the regulation of tumorigenesis and tumor cell migration and proliferation. microRNAs interact with target mRNA to silence gene expression and degrade mRNA, thereby inhibiting the expression of tumor genes or impairing the expression of tumor suppressor genes. Methods:A total of 20 human ESCC samples were collected from the Affiliated Tumor Hospital of Xinjiang Medical University. Eca109 and Kyse510 cells, which are ESCC cell lines, were subjected to FACS analysis to get side population (SP) cells and non-SP cells. Cell cycle and cell proliferation were analyzed by flow cytometry. Cell migration and invasion were detected using a transwell assay. Quantitative PCR and Western blot were performed to analyze the expression levels of ABCG2, KLF4, OCT4, and ACVR1, which are related to the stemness of stem cells. The target genes of hsa-miR-148a were predicted using TargetScan (version 7.2) and verified by a dual luciferase reporter assay. A chromatin immunoprecipitation (ChIP) assay was carried out to demonstrate direct interaction between miR-148a and ACVR1. Results:The expression of miR-148a was significantly down-regulated in ESCC cells and significantly decreased in SP esophageal squamous cells when compared to the tumor cells. By analyzing the stem cell stemness of ESCC, overexpression of miR-148a decreased the expression of ABCG2, KLF4, SOX2, OCT4, and Nanog, indicating that miR-148a may regulate stem cell function. Target gene prediction and functional annotation of miR-148a suggested that miR-148a is involved in stem cell stemness of ESCC via ACVR1. Expression of the dual luciferase-labeled gene indicates that overexpression of miR-148a inhibits the expression of ACVR1, thereby affecting stem cell stemness. Conclusion:miR-148a regulates the stem cell-like side populations distribution by inhibiting the expression of ACVR1 in ESCC. miR-148a may be a promising targeted therapy for ESCC.

SUBMITTER: Tan Y

PROVIDER: S-EPMC7457590 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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miR-148a Regulates the Stem Cell-Like Side Populations Distribution by Affecting the Expression of ACVR1 in Esophageal Squamous Cell Carcinoma.

Tan Yao Y Lu Xi X Cheng Zhenzhen Z Pan Guangpeng G Liu Shujuan S Apiziaji Palida P Wang Haifeng H Zhang Jinrong J Abulimiti Yisikandaer Y

OncoTargets and therapy 20200813

<h4>Introduction</h4>Esophageal squamous cell carcinoma (ESCC) is a malignant tumor disease with high mortality and morbidity rates, especially for a terminal cancer. At present, the prognosis and treatment of ESCC cannot effectively control or inhibit the spread and proliferation of tumor cells. microRNAs, a class of small spliced RNAs, are essential in the regulation of tumorigenesis and tumor cell migration and proliferation. microRNAs interact with target mRNA to silence gene expression and ...[more]

PMID: 32904700

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Project description:ObjectiveMiR-21 is an oncomir expressed by malignant cells and/or tumor microenvironment components. In this study we focused on understanding the effects of stromal miR-21 on esophageal malignant cells.DesignMiR-21 expression was evaluated in formalin-fixed paraffin-embedded samples from patients with esophageal squamous-cell carcinoma (SCC) by quantitative RT-PCR. MiR-21 tissue distribution was visualized with in situ hybridization. A co-culture system of normal fibroblasts and esophageal cancer cells was used to determine the effects of fibroblasts on miR-21 expression levels, and on SCC cell migration and invasion.ResultsMiR-21 was overexpressed in SCCs, when compared to the adjacent non-tumor tissues (P = 0.0007), and was mainly localized in the cytoplasm of stromal cells adjacent to malignant cells. Accordingly, miR-21 expression was increased in tumors with high versus low stromal content (P = 0.04). When co-cultured with normal fibroblasts, miR-21 expression was elevated in SCC cells (KYSE-30), while its expression was restricted to fibroblasts when co-cultured with adenocarcinoma cells (OE-33 and FLO-1). MiR-21 was detected in conditioned media of cancer cell lines, illustrating the release of this miRNA into the environment. Co-culturing with normal fibroblasts or addition of fibroblast conditioned media caused a significant increase in cell migration and invasion potency of KYSE-30 cells (P<0.0001). In addition, co-culturing cancer cells with fibroblasts and expression of miR-21 induced the expression of the cancer associated fibroblast (CAF) marker S100A4.ConclusionsMiR-21 expression is mostly confined to the SCC stroma and its release from fibroblasts influences the migration and invasion capacity of SCC cells. Moreover, miR-21 may be an important factor in "activating" fibroblasts to CAFs. These findings provide new insights into the role of CAFs and the extracellular matrix in tumor microenvironment formation and in tumor cell maintenance, and suggest miR-21 may contribute to cellular crosstalk in the tumor microenvironment.

Dataset Information

MiR-148a Regulates the Stem Cell-Like Side Populations Distribution by Affecting the Expression of ACVR1 in Esophageal Squamous Cell Carcinoma.

Publications

miR-148a Regulates the Stem Cell-Like Side Populations Distribution by Affecting the Expression of ACVR1 in Esophageal Squamous Cell Carcinoma.

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