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Exp Ther Med. 2017 Aug;14(2):1009-1016. doi: 10.3892/etm.2017.4590. Epub 2017 Jun 13.

MicroRNA-22 inhibits cell growth and metastasis in breast cancer via targeting of SIRT1.

Author information

1
Department of Breast Surgery, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China.
2
Department of Hepatobiliary and Endocrine Surgery, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China.
3
Department of General Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China.

Abstract

MicroRNAs (miRs), which are a class of small non-coding RNAs, are key regulators of gene expression via induction of translational repression or mRNA degradation. However, the molecular mechanism of miR-22 underlying the malignant progression of breast cancer, remains to be elucidated. The present study aimed to explore the regulatory mechanism of miR-22 in breast cancer cell growth and metastasis. Reverse transcription-quantitative polymerase chain reaction data revealed that miR-22 was significantly downregulated in breast cancer tissues, compared with adjacent non-tumor tissues. Furthermore, the miR-22 levels were further decreased in stage III-IV, compared with stage I-II breast cancer. In addition, low miR-22 levels were significantly associated with the poor differentiation, metastasis and advanced clinical stages of breast cancer. Sirtuin1 (SIRT1) was demonstrated to act as a direct target gene of miR-22 and its protein expression negatively regulated by miR-22 in the MCF-7 breast cancer cell line. Furthermore, SIRT1 expression levels were significantly upregulated in breast cancer tissues, compared with adjacent non-tumor tissues. SIRT1 levels were observed to be increased in stage III-IV when compared with stage I-II breast cancer. miR-22 overexpression decreased the proliferation, migration and invasion of MCF-7 cells, whereas overexpression of SIRT1 eliminated the suppressive effects of the miR-22 overexpression on the malignant phenotype of MCF-7 cells. The results of the present study therefore suggested that miR-22 demonstrated suppressive effects on breast cancer growth and metastasis via targeting SIRT1, and thus the miR-22/SIRT1 axis may be used as a novel and potential therapeutic target for breast cancer in the future.

KEYWORDS:

Sirtuin1; breast cancer; growth; metastasis; microRNA-22

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