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Am J Cancer Res. 2015 May 15;5(6):1939-53. eCollection 2015.

Transcription factor KLF4 regulates microRNA-544 that targets YWHAZ in cervical cancer.

Author information

1
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University Shanghai, China.
2
Department of Gynecology and Obstetrics, Changhai Hospital Shanghai, China.
3
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University Shanghai, China ; Shanghai Engineering Research Center of Industrial Microorganisms Shanghai, China.
4
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University Shanghai, China ; Shanghai Engineering Research Center of Industrial Microorganisms Shanghai, China ; Shanghai Collaborative Innovation Center for Biomanufacturing Technology Shanghai, China.

Abstract

The deregulation of microRNAs has been demonstrated in various tumor processes. Here, we report that microRNA-544 (miR-544) is decreased in cervical cancer tissues compared with normal cervical tissues. To identify the mechanisms involved in miR-544 deregulation, we studied the regulation of miR-544 expression at the transcriptional level. We first identified the transcriptional start site of miR-544 by 5' rapid amplification of cDNA ends and subsequently determined the miR-544 promoter. We discovered that the transcription factor Krueppel-like factor 4 (KLF4) is involved in the transcriptional regulation of miR-544 through interaction with the miR-544 promoter. In addition, we found that miR-544 directly targets the YWHAZ oncogene and functions as a tumor suppressor in cervical cancer cells. miR-544 is involved in cell cycle regulation and suppresses cervical cancer cell proliferation, colony formation, migration and invasion in a manner associated with YWHAZ downregulation. In summary, our findings demonstrate that KLF4 upregulates miR-544 transcription by activating the miR-544 promoter and that miR-544 functions as a tumor suppressor by targeting YWHAZ. Therefore, miR-544 may be a potential novel therapeutic target and prognostic marker for cervical cancer.

KEYWORDS:

KLF4; YWHAZ; cervical cancer; microRNA-544

PMID:
26269755
PMCID:
PMC4529615

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