Zhao Dongli, Sui Yanxia, Zheng Xiaoqiang
Department of Radiotherapy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Oncol Rep. 2016 Feb;35(2):1075-82. doi: 10.3892/or.2015.4450. Epub 2015 Nov 26.
MicroRNAs (miRNAs) regulate cell proliferation, apoptosis and carcinogenesis by targeting related mRNAs in different types of cancer. miR-331-3p has been found to regulate the development and progression of various types of cancer cells. However, little research has been conducted on the role of miR-331-3p in colorectal cancer (CRC). The present study aimed to explore the function of miR-331-3p in CRC. We found that miR-331-3p was significantly downregulated in CRC tissues and cells compared to the level in healthy colon tissues and cells. Overexpression of miR-331-3p by transfection with pre‑miR-331-3p inhibited cell proliferation, promoted apoptosis and activated caspase-3. Furthermore, the protein expression level of apoptosis-related protein Bcl-2 was downregulated and Bax was upregulated by pre‑miR‑331-3p. Downregulation of the expression of miR-331-3p by transfection with AS-miR-331-3p had the opposite effect. Moreover, we found that HER2 was overexpressed in the CRC cell lines, and the expression level of HER2 was negatively regulated by miR‑331-3p. Additionally, knockdown of HER2 inhibited cell proliferation and phosphorylation of Akt and ERK1/2 induced by AS-miR-331-3p. Overall, we identified that miR‑331-3p is underexpressed in CRC and contributes to cell growth regulation by targeting HER2 through activating the PI3K/Akt and ERK1/2 signaling pathways.
微小RNA（miRNA）通过靶向不同类型癌症中的相关信使核糖核酸（mRNA）来调节细胞增殖、凋亡和致癌作用。已发现miR-331-3p可调节各种类型癌细胞的发生和发展。然而，关于miR-331-3p在结直肠癌（CRC）中的作用的研究较少。本研究旨在探讨miR-331-3p在CRC中的功能。我们发现，与健康结肠组织和细胞中的水平相比，miR-331-3p在CRC组织和细胞中显著下调。通过转染pre-miR-331-3p过表达miR-331-3p可抑制细胞增殖、促进凋亡并激活半胱天冬酶-3。此外，pre-miR-331-3p可下调凋亡相关蛋白Bcl-2的蛋白表达水平并上调Bax。通过转染AS-miR-331-3p下调miR-331-3p的表达则产生相反的效果。此外，我们发现HER2在CRC细胞系中过表达，且HER2的表达水平受到miR-331-3p的负调控。另外，敲低HER2可抑制AS-miR-331-3p诱导的细胞增殖以及Akt和ERK1/2的磷酸化。总体而言，我们确定miR-331-3p在CRC中表达不足，并通过激活PI3K/Akt和ERK1/2信号通路靶向HER2来促进细胞生长调节。
