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BMC Cancer. 2019 Mar 8;19(1):209. doi: 10.1186/s12885-019-5400-3.

MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway.

Lu L1,2, Liu Q1,2, Wang P1,2, Wu Y1,2, Liu X1,2, Weng C1,2, Fang X1,2, Li B1,2, Cao X1,2, Mao H1,2, Wang L1,2, Guan M3,4, Wang W5, Liu G6,7.

Author information

1
Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China.
2
Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China.
3
Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. 13808815499@163.com.
4
Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. 13808815499@163.com.
5
Department of Experimental Research and State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, 510080, Guangdong, China. wangwei@sysucc.org.cn.
6
Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. eyglliu@scut.edu.cn.
7
Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. eyglliu@scut.edu.cn.

Abstract

BACKGROUND:

MicroRNA-148b (miR-148b) has been detected in various types of tumors, and is generally viewed as a tumor suppressor. Our previous study found the decreased expression of miR-148b in human non small cell lung cancer (NSCLC) specimens and cell lines. However, the underlying mechanisms of miR-148b in regulating tumor progression remain unclear.

METHODS:

Firstly animal experiments were performed to verify whether miR-148b could inhibit the tumor growth. Then, the underlying mechanisms were studied by transfecting recombinant plasmids containing a miR-148b mimic or a negative control (NC) mimic (shRNA control) into NSCLC cell lines PC14/B and A549 cells. Tumor cells transfected with unpackaged lentiviral vectors was used as blank control. Cell proliferation capabilities were measured by using CCK-8 kit and colony formation assay. Cell cycle arrest was compared to clarify the mechanism underlying the tumor cell proliferation. Annexin V-FITC Apoptosis Detection kit was applied to investigate the effect of miR-148b on cell apoptosis. Furthermore, western blot analysis were performed to study the targeting pathway.

RESULTS:

We found that over-expression of miR148b could significantly inhibit tumor growth, while knocking down miR148b could obviously promote tumor growth. Further experiment showed that miR-148b inhibited tumor cell proliferation. Besides, over-expression of miR148b decreased the G2/M phase population of the cell cycle by preventing NSCLC cells from entering the mitotic phase and enhanced tumor cell apoptosis. Further western blot analysis indicated that miR148b could inhibit mitogen-activated protein kinase/Jun N-terminal kinase (MAPK/JNK) signaling by decreasing the expression of phosphorylated (p) JNK.

CONCLUSIONS:

These results demonstrate that miR-148b could inhibit the tumor growth and act as tumor suppressor by inhibiting the proliferation and inducing apoptosis of NSCLC cells by blocking the MAPK/JNK pathway.

KEYWORDS:

Apoptosis; MAPK/JNK pathway; Non small cell lung cancer (NSCLC);tumor suppressor; Proliferation; microRNA-148b

PMID:
30849960
DOI:
10.1186/s12885-019-5400-3
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