miR‑1273g‑3p promotes proliferation, migration and invasion of LoVo cells via cannabinoid receptor 1 through activation of ERBB4/PIK3R3/mTOR/S6K2 signaling pathway

Li,Min; Qian,Xiaoping; Zhu,Mingzhen; Li,Aiyi; Fang,Mingzhi; Zhu,Yong; Zhang,Jingyu

doi:10.3892/mmr.2018.8397

miR‑1273g‑3p promotes proliferation, migration and invasion of LoVo cells via cannabinoid receptor 1 through activation of ERBB4/PIK3R3/mTOR/S6K2 signaling pathway

Authors:
- Min Li
- Xiaoping Qian
- Mingzhen Zhu
- Aiyi Li
- Mingzhi Fang
- Yong Zhu
- Jingyu Zhang
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Affiliations: Department of Oncology, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China, Department of The Comprehensive Cancer Center, Affiliated Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu 210008, P.R. China, The Department of Tumor‑Chemotherapy, The Second People's Hospital of Lianyungang, Lianyungang, Jiangsu 222023, P.R. China, National Medical Centre of Colorectal Disease, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China
Published online on: January 9, 2018 https://doi.org/10.3892/mmr.2018.8397
Pages: 4619-4626

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Abstract

MicroRNAs (miR) are important in various crucial cell processes including proliferation, migration and invasion. Dysregulation of miRNAs have been increasingly reported to contribute to colorectal cancer. However, the detailed biological function and potential mechanisms of miR‑1273g‑3p in colorectal cancer remain poorly understood. The expression levels of miR‑1273g‑3p in human colorectal cancer LoVo cell lines were detected via reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The target genes of miR‑1273g‑3p were predicted by bioinformatics and verified by a luciferase reporter assay, RT‑qPCR and western blotting. The MTT, wound‑healing and Transwell assays were used to examine the biological functions of miR‑1273g‑3p in LoVo cells. The potential molecular mechanisms of miR‑1273g‑3p on LoVo cell proliferation, migration and invasion was detected by western blotting. The results of the present study demonstrated that miR‑1273g‑3p expression was extensively upregulated in LoVo cells compared with the normal colon epithelial NCM460 cell line. Further studies indicated that miR‑1273g‑3p inhibitor significantly suppressed LoVo cell proliferation, migration and invasion compared with inhibitor control. Following this, the cannabinoid receptor 1 (CNR1) was identified as a direct target gene of miR‑1273g‑3p. Knockdown of CNR1 restored the phenotypes of LoVo cells transfected with miR‑1273g‑3p inhibitor. Furthermore, the potential molecular mechanism of miR‑1273g‑3p on LoVo cell proliferation, migration and invasion may be mediated by activating the Erb‑B2 receptor tyrosine kinase 4 (ERBB4)/phosphoinositide‑3‑kinase regulatory subunit 3 (PIK3R3)/mechanistic target of rapamycin (mTOR)/S6 kinase 2 (S6K2) signaling pathway. These observations indicated that miR‑1273g‑3p promoted the proliferation, migration and invasion of LoVo cells via CNR1, and this may have occurred through activation of the ERBB4/PIK3R3/mTOR/S6K2 signaling pathway, suggesting that miR‑1273g‑3p may serve as a novel therapeutic target for the effective treatment of colorectal cancer.

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