Zhang Guochao, Zhong Lele, Luo Hao, Wang Shibing
Department of Breast and Thyroid Surgery, Affiliated Jining No. 1 People's Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272011, People's Republic of China.
Onco Targets Ther. 2019 Sep 27;12:7993-8002. doi: 10.2147/OTT.S206180. eCollection 2019.
BACKGROUND/PURPOSE: Cell adhesion molecule 1 (CADM1) functions as a tumor suppressor and has been identified to be frequently inactivated in breast cancer, and closely associated with patients' poor prognosis and advanced TNM stage. However, the mechanisms underlying CADM1 in breast cancer progression remains incompletely clear. miR-155, a predicted modulator of CADM1 was reported to be overexpressed in breast cancer, and its high expression level was closely related to the malignant progression of breast cancer. The present study aimed to explore whether miR-155-3p could modulate CADM1 expression and then involved in the progression of breast cancer.
The expression patterns of miR-155-3p in breast cancer tissues and cell lines were determined by RT-PCR technology. The relationship between CADM1 and miR-155-3p were determined by the luciferase gene reporter and Western Blot (WB) assays. Cell proliferation, apoptosis rates and tumorigenesis were determined by CCK-8, flow cytometry and in vivo xenotransplanation experiments, respectively.
miR-155-3p was up-regulated in breast cancer tissues and cells when compared to the adjacent normal tissues and normal breast MCF 10A cells. The mRNA and protein levels of CADM1 showed opposite expression patterns to that of miR-155-3p expression detected, and miR-155-3p could negatively regulate CADM1 expression in breast cancer MCF-7 cells. Moreover, gain-of function assay showed that overexpression of miR-155-3p promoted cell proliferation, tumorigenesis and repressed cell apoptosis, but these effects were all significantly impaired when the cells were simultaneously transfected with OE-CADM1, the overexpressing vector of CADM1.
This study revealed that miR-155-3p could accelerate the progression of breast cancer via down-regulation of CADM1 expression.
背景/目的:细胞黏附分子1(CADM1)作为一种肿瘤抑制因子,已被证实其在乳腺癌中常发生失活,且与患者的不良预后及晚期TNM分期密切相关。然而,CADM1在乳腺癌进展中的潜在机制仍不完全清楚。据报道,miR-155作为CADM1的一种预测调节因子,在乳腺癌中呈过表达,其高表达水平与乳腺癌的恶性进展密切相关。本研究旨在探讨miR-155-3p是否能调节CADM1的表达,进而参与乳腺癌的进展。
采用RT-PCR技术检测miR-155-3p在乳腺癌组织和细胞系中的表达模式。通过荧光素酶基因报告实验和蛋白质免疫印迹(WB)实验确定CADM1与miR-155-3p之间的关系。分别通过CCK-8实验、流式细胞术和体内异种移植实验检测细胞增殖、凋亡率和肿瘤发生情况。
与相邻正常组织和正常乳腺MCF 10A细胞相比,miR-155-3p在乳腺癌组织和细胞中表达上调。CADM1的mRNA和蛋白水平与检测到的miR-155-3p表达呈相反的表达模式,且miR-155-3p可在乳腺癌MCF-7细胞中负向调节CADM1的表达。此外,功能获得实验表明,miR-155-3p的过表达促进细胞增殖、肿瘤发生并抑制细胞凋亡,但当细胞同时转染CADM1过表达载体OE-CADM1时,这些作用均受到显著抑制。
本研究表明,miR-155-3p可通过下调CADM1的表达加速乳腺癌的进展。