Open Access

ARTICLE

MicroRNA-338-3p Inhibits Proliferation and Promotes Apoptosis of Multiple Myeloma Cells Through Targeting Cyclin-Dependent Kinase 4

Yang Cao^*, Xu Shi^†, Yingmin Liu^‡, Ren Xu^§, Qing Ai^*

* Clinical Laboratory, the First Affiliated Hospital, Jilin University, Chaoyang District, Changchun, P.R. China
† Central Laboratory, the First Affiliated Hospital, Jilin University, Chaoyang District, Changchun, P.R. China
‡ Department of Hematology Cancer Center, the First Affiliated Hospital, Jilin University, Chaoyang District, Changchun, P.R. China
§ Department of Respiratory, the First Affiliated Hospital, Jilin University, Chaoyang District, Changchun, P.R. China

Oncology Research 2019, 27(1), 117-124. https://doi.org/10.3727/096504018X15213031799835

Abstract

MicroRNA-338-3p (miR-338-3p) has been reported to be a tumor suppressor in multiple cancer types. However, the biological role of miR-338-3p and its underlying mechanism in multiple myeloma (MM) remain unclear. In the present study, we investigated the biological role and potential of miR-338-3p in MM. We found that miR-338-3p was significantly decreased in newly diagnosed and relapsed MM tissues and cell lines. Overexpression of miR-338-3p in MM cells significantly inhibited proliferation and promoted apoptosis, caspase 3, and caspase 8 activity. Bioinformatics algorithm analysis predicted that cyclin-dependent kinase 4 (CDK4) was a direct target of miR-338-3p, and this was experimentally verified by a dual-luciferase reporter assay. Furthermore, overexpression of miR-338-3p inhibited CDK4 expression on mRNA and protein levels. Of note, the restoration of CDK4 expression markedly abolished the effect of miR-338-3p overexpression on cell proliferation, apoptosis, caspase 3, and caspase 8 activities in MM cells. Taken together, the present study is the first to demonstrate that miR-338-3p functions as a tumor suppressor in MM through inhibiting CDK4. This finding implies that miR-338-3p is a potential therapeutic target for the treatment of MM.

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