The microRNA-302-367 cluster suppresses the proliferation of cervical carcinoma cells through the novel target AKT1

  1. Peng-Sheng Zheng1,2,3,4
  1. 1Department of Reproductive Medicine, First Affiliated Hospital, Xi'an Jiaotong University Medical School, Xi'an 710061, The People's Republic of China
  2. 2Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Medical School, Xi'an 710061, The People's Republic of China
  3. 3Division of Cancer Stem Cell Research, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University Medical School, Xi'an 710061, The People's Republic of China

    Abstract

    The miR-302-367 cluster is specifically expressed in human embryonic stem cells and has been shown to convert human somatic cells into induced pluripotent stem cells. Here, we investigated the role of the miR-302-367 cluster in cervical carcinoma. The cluster was not endogenously expressed in cervical cancer cells, and its ectopic expression did not reprogram the cervical cancer cells to an embryonic stem cell-like state. However, ectopic expression of the miR-302-367 cluster in HeLa and SiHa cervical cancer cells inhibited cell proliferation and tumor formation by blocking the G1/S cell cycle transition. We identified a new cell cycle regulatory pathway in which the miR-302-367 cluster directly down-regulated both cyclin D1 and AKT1 and indirectly up-regulated p27Kip1 and p21Cip1, leading to the suppression of cervical cancer cell proliferation. Our findings suggest that the miR-302-367 cluster may be used as a therapeutic reagent for the treatment of cervical carcinoma.

    Keywords

    Footnotes

    • Received June 27, 2012.
    • Accepted October 28, 2012.
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