Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics*
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Adenocarcinoma / pathology
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Apoptosis / physiology
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Caspase 3 / metabolism
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Cell Division
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Cell Line, Tumor
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Colorectal Neoplasms / genetics*
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Colorectal Neoplasms / pathology
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Enzyme Activation / genetics
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Gene Expression Regulation, Neoplastic / genetics*
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Genes, bcl-2
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Genes, erbB-2
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Humans
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MAP Kinase Signaling System / genetics
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MicroRNAs / biosynthesis
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MicroRNAs / genetics*
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology
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Phosphatidylinositol 3-Kinases / physiology
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Phosphorylation / genetics
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Protein Processing, Post-Translational / genetics
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Proto-Oncogene Proteins c-akt / physiology
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Proto-Oncogene Proteins c-bcl-2 / genetics
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RNA Precursors / genetics
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RNA, Antisense / genetics
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RNA, Neoplasm / biosynthesis
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RNA, Neoplasm / genetics*
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Receptor, ErbB-2 / biosynthesis
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Receptor, ErbB-2 / physiology*
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Signal Transduction / genetics*
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Transfection
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bcl-2-Associated X Protein / biosynthesis
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bcl-2-Associated X Protein / genetics
Substances
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BAX protein, human
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MIRN331 microRNA, human
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MicroRNAs
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Neoplasm Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA Precursors
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RNA, Antisense
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RNA, Neoplasm
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bcl-2-Associated X Protein
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Phosphatidylinositol 3-Kinases
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ERBB2 protein, human
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Receptor, ErbB-2
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AKT1 protein, human
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Proto-Oncogene Proteins c-akt
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CASP3 protein, human
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Caspase 3