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MiR-34a Inhibits Viability and Invasion of Human Papillomavirus–Positive Cervical Cancer Cells by Targeting E2F3 and Regulating Survivin
  1. Dianzhong Geng, MD*,
  2. Xiaohua Song, MD,
  3. Fangling Ning, PhD*,
  4. Qianhua Song, BS and
  5. Honghua Yin, BS
  1. *Department of Oncology, Binzhou Medical University Hospital;
  2. Department of Obstetrics and Gynecology, Binzhou People’s Hospital; and
  3. Department of Obstetrics and Gynecology, Zouping Maternal and Child Health-Care Hospital, Shandong, China.
  1. Address correspondence and reprint requests to Fangling Ning, PhD, Department of Oncology, Binzhou Medical University Hospital, No. 661, Huanghe 2nd Rd, Binzhou, Shandong 256603, China. E-mail: Fanglingning{at}163.com.

Abstract

Objective Previous studies confirmed that high-risk human papillomavirus (HR-HPV) infection is a risk factor of cervical cancer, and the infection was associated with significantly reduced miR-34a expression during carcinogenesis. However, the downstream targets of miR-34a and their roles are still not well understood. This study explored the regulative role of miR-34a on E2F3 and survivin expression and the viability and invasion of HPV-positive cervical cancer cells.

Methods MiR-34a and survivin expression in 56 cases of HR-HPV–positive patients, 28 cases of HR-HPV–negative patients, and 28 normal cases without HR-HPV infections were measured. Human papillomavirus-18–positive HeLa cervical cancer cells and HPV-16–positive SiHa cells were used to explore the effect of miR-34a on cell viability and invasion. The molecular target of miR-34a was also explored in cervical cancer cells.

Results The results showed that miR-34a overexpression could inhibit HPV-positive cancer cell viability, whereas its downregulation promoted cell viability. E2F3 is a direct target of miR-34a in HPV-positive cervical cancer cells. By targeting E2F3, miR-34a could regulate the expression of survivin. Thus, through regulating E2F3 and survivin, miR-34a could reduce the viability and invasion of HPV-positive cervical cancer cells.

Conclusions This study confirmed a novel miR-34a–E2F3–survivin axis in the tumor suppressor role of miR-34a in cervical cancer.

  • Human papillomavirus
  • Cervical cancer
  • MiR-34a
  • E2F3
  • Survivin

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Footnotes

  • Dianzhong Geng and Xiaohua Song contributed equally to this work.

  • The authors declare no conflicts of interest.

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