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Reduced miR-34a Expression in Normal Cervical Tissues and Cervical Lesions With High-Risk Human Papillomavirus Infection
  1. Baohua Li, PhD*,
  2. Ying Hu, PhD*,
  3. Feng Ye, PhD*,
  4. Yang Li, PhD*,
  5. Weiguo Lv, MD*, and
  6. Xing Xie, MD*,
  1. *Women's Reproductive Health Key Laboratory of Zhejiang Province; and
  2. Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  1. Address correspondence and reprint requests to Xing Xie, MD, Department of Gynecologic Oncology, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Xueshi Rd no. 2, Hangzhou, 310006, China. E-mail: xiex{at}mail.hz.zj.cn.

Abstract

Introduction: Reduced miR-34a expression is associated with high-risk human papillomavirus (HR-HPV) infection and cervical cancer. Whether the reduction of miR-34a expression induced by HR-HPV E6 occurs in precancerous lesions, even before morphologic change, is still uncertain. Our study aimed to ascertain the possibility of pri-miR-34a involved in the development of cervical lesions and to explore the mechanism of altered pri-miR-34a expression induced by HPV-16 E6.

Methods: The levels of pri-miR-34a expression were examined in different cervical tissues, including normal cervical epithelium with (n = 32) or without (n = 32) HR-HPV infection, cervical intraepithelial neoplasia (CIN) with (n = 32) or without (n = 12) HR-HPV infection, and cervical cancer (n = 32), by semiquantitative reverse transcription-polymerase chain reaction. The HPV-16 E6 expression vector and HPV-16 E6 small interfering RNAs were conducted and transfected into 293T cells and SiHa cells, respectively. The expression of pri-miR-34a and p53 protein was simultaneously analyzed by reverse transcription-polymerase chain reaction and Western blot in cells with gene transfection and without.

Results: pri-miR-34a expression was significantly reduced in CIN and cervical cancer compared with normal cervical epithelium, as well as in CIN 2 and CIN 3 compared with CIN I. Moreover, the expression of pri-miR-34a was significantly lower in normal cervical epithelium and CIN with HR-HPV infection than in those without. Simultaneous down-regulation or up-regulation of pri-miR-34a and p53 expression was observed in E6-transfected 293T cells or E6 small interfering RNA-transferred SiHa cells compared with controls.

Conclusions: Reduced expression of pri-miR-34a occurs not only in cervical cancer but also in precancerous lesion even before morphologic change. The inhibition of miR-34a expression induced by HR-HPV E6 in the p53-dependent pathway is probably an early-onset event in the development of cervical cancer.

  • Human papillomavirus
  • Primary-miR-34a
  • p53 protein
  • Cervical carcinogenesis

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Footnotes

  • Baohua Li and Ying Hu contributed equally to this work.

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