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

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.

journal_name

BMC Cancer

journal_title

BMC cancer

authors

Lu L,Liu Q,Wang P,Wu Y,Liu X,Weng C,Fang X,Li B,Cao X,Mao H,Wang L,Guan M,Wang W,Liu G

doi

10.1186/s12885-019-5400-3

subject

Has Abstract

pub_date

2019-03-08 00:00:00

pages

209

issue

issn

1471-2407

pii

10.1186/s12885-019-5400-3

journal_volume

pub_type

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