miR-367 promotes tumor growth by inhibiting FBXW7 in NSCLC

Xiao,Guodong; Gao,Xiao; Sun,Xin; Yang,Chengcheng; Zhang,Boxiang; Sun,Ruiying; Huang,Guanghong; Li,Xiang; Liu,Jian; Du,Ning; Liu,Dapeng; Liang,Rui; Ren,Hong; Qin,Sida

doi:10.3892/or.2017.5755

miR-367 promotes tumor growth by inhibiting FBXW7 in NSCLC

Authors:
- Guodong Xiao
- Xiao Gao
- Xin Sun
- Chengcheng Yang
- Boxiang Zhang
- Ruiying Sun
- Guanghong Huang
- Xiang Li
- Jian Liu
- Ning Du
- Dapeng Liu
- Rui Liang
- Hong Ren
- Sida Qin
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Affiliations: Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China, Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China, Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China, Department of Hepatobiliary Chest Surgery, Shaanxi Provincial Corps Hospital of Chinese People's Armed Police Force, Taiyuan, Shanxi, P.R. China
Published online on: June 27, 2017 https://doi.org/10.3892/or.2017.5755
Pages: 1190-1198

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Abstract

miR-367 is one of the most abundant miRNAs in human embryonic stem cells (hESCs) and is mainly involved in maintaining the pluripotency of stem cells. However, its role in cancer development remains poorly understood. In the present study, we explored the function and mechanism of the endogenous miR-367 in non-small cell lung cancer (NSCLC). In the present study, we demonstrated that the level of miR-367 in NSCLC was significantly higher than that in adjacent normal tissues, and its upregulation was positively correlated with tumor size, tumor differentiation and tumor-node-metastasis (TNM) stage. miR-367 was an indicator of a poorer prognosis in NSCLC patients. Furthermore, overexpression of miR-367 significantly inhibited apoptosis and enhanced proliferation by promoting cell cycle transition from G1 to S phase. In contrast, knockdown of miR-367 markedly reversed the cellular events observed with miR-367 overexpression. Moreover, we identified that F-box and WD repeat domain-containing 7 (FBXW7) is a novel target of miR-367. It reverses the oncogenic effects of miR-367 by downregulating its substrates, c-Myc and c-Jun, in NSCLC cells. Finally, studies in vivo revealed that knockdown of miR-367 inhibited the growth of xenografts in the nude mice by increasing the expression of FBXW7. In summary, our findings indicate that miR-367 exerts tumor-promoting effect by negatively regulating FBXW7 in NSCLC, and it could become a potential therapeutic target for NSCLC intervention.

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