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FEBS J. 2019 Apr 3. doi: 10.1111/febs.14835. [Epub ahead of print]

MicroRNA-520c-3p functions as a novel tumor suppressor in lung adenocarcinoma.

Li X1,2,3,4, Fu Q1,2,3,4, Li H2,4,5,6, Zhu L1,2,3,4, Chen W1,2,3,4, Ruan T7, Xu W1,2,3,4, Yu X1,2,3,4.

Author information

1
Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, China.
2
National Clinical Research Center for Cancer, Tianjin, China.
3
Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
4
Tianjin's Clinical Research Center for Cancer, China.
5
Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
6
Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, China.
7
Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

Abstract

Lung cancer is a malignancy with one of the highest incidence rates, and it is the leading cause of cancer-related death. To gain further insights into the underlying mechanisms of tumor growth and metastasis, we investigated the role and expression of microRNAs in lung adenocarcinoma (LUAD). We discovered a significantly lower expression level of microRNA-520c-3p (miR-520c-3p) in LUAD tissues than in nontumor tissues. miR-520c-3p is known to regulate multiple biological functions and cellular behaviors. In this study, we show that AKT1 and AKT2 are key direct targets of miR-520c-3p, which are required for its biological roles in LUAD. Mechanistically, downregulation of miR-520c-3p in LUAD is due to DNA methylation of the miR-520c-3p promoter region. Conversely, the activity of the transcription factor Yin Yang 1 (YY1) results in the upregulation of miR-520c-3p. Taken together, our results reveal methylation/YY1/miR-520c-3p/AKT1/AKT2 as a molecular axis with a potent biological function and highlight miR-520c-3p as a novel potent tumor suppressor in LUAD.

KEYWORDS:

AKT; YY1; lung adenocarcinoma; methylation; microRNA

PMID:
30942957
DOI:
10.1111/febs.14835

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