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Biochem Biophys Res Commun. 2015 Apr 17;459(4):679-85. doi: 10.1016/j.bbrc.2015.03.004. Epub 2015 Mar 11.

miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1.

Author information

1
Cangzhou Central Hospital, Hebei 061001, China.
2
Cangzhou Central Hospital, Hebei 061001, China. Electronic address: commasll@163.com.

Abstract

Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3'-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity.

KEYWORDS:

Cervical cancer; HR-HPV; Radioresistance; miR-21

PMID:
25769949
DOI:
10.1016/j.bbrc.2015.03.004
[Indexed for MEDLINE]

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