MiR-375 Modulates Radiosensitivity of HR-HPV-Positive Cervical Cancer Cells by Targeting UBE3A Through the P53 Pathway

Overview

Journal Med Sci Monit

Specialties General Medicine
Pathology

Date 2015 Jul 31

PMID 26224081

Citations 19

Authors

Lili Song

Shikai Liu

Saitian Zeng

Liang Zhang

Xia Li

Affiliations

Soon will be listed here.

Abstract

Background: Prediction of radioresistance of HR-HPV-positive (+) cervical cancer, especially before the course of radiotherapy, is quite beneficial to develop an optimal treatment strategy for individual patients. Unfortunately, the mechanisms responsible for radioresistance of cervical cancer are still largely unexplored. HR-HPV infection leads to a series of changes to normal biophysical process, including miRNAs expression. In this study, we explored the association between miR-375 and radioresistance in HR-HPV (+) cervical cancer.

Material And Methods: qRT-PCR analysis was performed to determine miR-375 expression in HR-HPV-positive (+) cervical cancer patients and in HPV-16-positive SiHa and HPV-18-positive HeLa cervical cancer cell lines. The influence of miR-375 on radiosensitivity and the downstream regulative network were further explored in the cell line models.

Results: The results verified a putative binding site between miR-375 and UBE3A. miR-375 overexpression could significantly reduce UBE3A expression. UBE3A knockdown led to significantly reduced cell survival under radiation treatment. miR-375 promoted radiosensitivity of HR-HPV (+) cancer through decreasing p53 degradation and thereby increasing radiation-induced apoptosis.

Conclusions: The miR-375-UBE3A axis is important in modulating radiosensitivity of HR-HPV (+) cervical cancer.

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References

Ke G, Liang L, Yang J, Huang X, Han D, Huang S . MiR-181a confers resistance of cervical cancer to radiation therapy through targeting the pro-apoptotic PRKCD gene. Oncogene. 2012; 32(25):3019-27. DOI: 10.1038/onc.2012.323. View

Koh W, Greer B, Abu-Rustum N, Apte S, Campos S, Chan J . Cervical cancer. J Natl Compr Canc Netw. 2013; 11(3):320-43. DOI: 10.6004/jnccn.2013.0043. View

Jung H, Phillips B, Chan E . miR-375 activates p21 and suppresses telomerase activity by coordinately regulating HPV E6/E7, E6AP, CIP2A, and 14-3-3ζ. Mol Cancer. 2014; 13:80. PMC: 4021670. DOI: 10.1186/1476-4598-13-80. View

Powell M . Modern radiotherapy and cervical cancer. Int J Gynecol Cancer. 2010; 20(11 Suppl 2):S49-51. DOI: 10.1111/igc.0b013e3181f7b241. View

Shen Y, Zhou J, Li Y, Ye F, Wan X, Lu W . miR-375 mediated acquired chemo-resistance in cervical cancer by facilitating EMT. PLoS One. 2014; 9(10):e109299. PMC: 4199595. DOI: 10.1371/journal.pone.0109299. View

Sah N, Khan Z, Khan G, Bisen P . Structural, functional and therapeutic biology of survivin. Cancer Lett. 2006; 244(2):164-71. DOI: 10.1016/j.canlet.2006.03.007. View

Frega A, Sopracordevole F, Scirpa P, Biamonti A, Lorenzon L, Scarani S . The re-infection rate of high-risk HPV and the recurrence rate of vulvar intraepithelial neoplasia (VIN) usual type after surgical treatment. Med Sci Monit. 2011; 17(9):CR532-5. PMC: 3560503. DOI: 10.12659/msm.881941. View

Dunne E, Park I . HPV and HPV-associated diseases. Infect Dis Clin North Am. 2013; 27(4):765-78. DOI: 10.1016/j.idc.2013.09.001. View

Rogers L, Siu S, Luesley D, Bryant A, Dickinson H . Radiotherapy and chemoradiation after surgery for early cervical cancer. Cochrane Database Syst Rev. 2012; (5):CD007583. PMC: 4171000. DOI: 10.1002/14651858.CD007583.pub3. View

10.

Durst M, Gissmann L, Ikenberg H, zur Hausen H . A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A. 1983; 80(12):3812-5. PMC: 394142. DOI: 10.1073/pnas.80.12.3812. View

11.

Beskow C, Skikuniene J, Holgersson A, Nilsson B, Lewensohn R, Kanter L . Radioresistant cervical cancer shows upregulation of the NHEJ proteins DNA-PKcs, Ku70 and Ku86. Br J Cancer. 2009; 101(5):816-21. PMC: 2736845. DOI: 10.1038/sj.bjc.6605201. View

12.

Concin N, Zeillinger C, Stimpfel M, Schiebel I, Tong D, Wolff U . p53-dependent radioresistance in ovarian carcinoma cell lines. Cancer Lett. 2000; 150(2):191-9. DOI: 10.1016/s0304-3835(99)00393-6. View

13.

Yang C, Peng L, Huang T, Yang G, Chu Q, Liang Y . Cancer stem-like cell characteristics induced by EB virus-encoded LMP1 contribute to radioresistance in nasopharyngeal carcinoma by suppressing the p53-mediated apoptosis pathway. Cancer Lett. 2013; 344(2):260-71. DOI: 10.1016/j.canlet.2013.11.006. View

14.

Bartel D . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97. DOI: 10.1016/s0092-8674(04)00045-5. View

15.

Liu Y, Xing R, Zhang X, Dong W, Zhang J, Yan Z . miR-375 targets the p53 gene to regulate cellular response to ionizing radiation and etoposide in gastric cancer cells. DNA Repair (Amst). 2013; 12(9):741-50. DOI: 10.1016/j.dnarep.2013.06.002. View

16.

Hong S, Noh H, Teng Y, Shao J, Rehmani H, Ding H . SHOX2 is a direct miR-375 target and a novel epithelial-to-mesenchymal transition inducer in breast cancer cells. Neoplasia. 2014; 16(4):279-90.e1-5. PMC: 4094831. DOI: 10.1016/j.neo.2014.03.010. View

17.

Scheffner M, Huibregtse J, Vierstra R, Howley P . The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell. 1993; 75(3):495-505. DOI: 10.1016/0092-8674(93)90384-3. View

18.

Li Y, Wang F, Xu J, Ye F, Shen Y, Zhou J . Progressive miRNA expression profiles in cervical carcinogenesis and identification of HPV-related target genes for miR-29. J Pathol. 2011; 224(4):484-95. DOI: 10.1002/path.2873. View

19.

Xu Y, Jin J, Liu Y, Huang Z, Deng Y, You T . Snail-regulated MiR-375 inhibits migration and invasion of gastric cancer cells by targeting JAK2. PLoS One. 2014; 9(7):e99516. PMC: 4108470. DOI: 10.1371/journal.pone.0099516. View

20.

Waggoner S . Cervical cancer. Lancet. 2003; 361(9376):2217-25. DOI: 10.1016/S0140-6736(03)13778-6. View