Downregulation of microRNA‑33a promotes cyclin‑dependent kinase 6, cyclin D1 and PIM1 expression and gastric cancer cell proliferation

Wang,Yudong; Zhou,Xinliang; Shan,Baoen; Han,Jing; Wang,Feifei; Fan,Xiaojie; Lv,Yalei; Chang,Liang; Liu,Wei

doi:10.3892/mmr.2015.4296

Downregulation of microRNA‑33a promotes cyclin‑dependent kinase 6, cyclin D1 and PIM1 expression and gastric cancer cell proliferation

Authors:
- Yudong Wang
- Xinliang Zhou
- Baoen Shan
- Jing Han
- Feifei Wang
- Xiaojie Fan
- Yalei Lv
- Liang Chang
- Wei Liu
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Affiliations: Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
Published online on: September 7, 2015 https://doi.org/10.3892/mmr.2015.4296
Pages: 6491-6500
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although microRNA‑33 (miR‑33) family members are known to be involved in the regulation and balancing of cholesterol metabolism, fatty acid oxidation and insulin signaling, their functions in carcinogenesis are controversial and the underlying mechanisms have remained elusive. Gastric cancer is the fourth most common malignancy in the world; however, the dysregulation and function of miR‑33 family members in gastric cancer have not been extensively studied. The present study reported that a miR‑33 family member, miR‑33a, was significantly downregulated in gastric cancer tissues and gastric cancer cell lines. Of note, the expression of miR‑33a was inversely correlated with pathological differentiation and metastasis as well as gastric cancer biomarker CA199. A cell‑counting kit‑8 assay showed that transfection of the SGC‑7901 gastric cell line with miR‑33a‑overexpression plasmid inhibited the capability of the cells to proliferate. Furthermore, overexpression of miR‑33a led to cell cycle arrest of SGC‑7901 cells in G1 phase. In addition, a luciferase reporter assay showed that miR‑33a directly targeted cyclin‑dependent kinase 6 (CDK6), cyclin D1 (CCND1) and serine/threonine kinase PIM‑1. In gastric cancer specimens, the reduced expression of miR‑33a was associated with increased expression of CDK‑6, CCND1 and PIM1. However, only PIM1 expression was significantly increased in cancer tissues compared with that in their adjacent tissues. The present study revealed that miR‑33a was downregulated in gastric cancer tissues and cell lines, while forced overexpression of miR‑33a decreased CDK‑6, CCND1 and PIM1 expression to inhibit gastric cancer cell proliferation by causing G1 phase arrest. miR‑33a overexpression may therefore resemble an efficient strategy for gastric cancer therapy.

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