Knockdown of long non-coding RNA HOST2 inhibits the proliferation of triple negative breast cancer via regulation of the let-7b/CDK6 axis

  • Authors:
    • Yuedong Zhang
    • Hongwei Zhang
    • Huiqing Kang
    • Wenjie Huo
    • Yu Zhou
    • Yuchao Zhang
  • View Affiliations

  • Published online on: November 26, 2018     https://doi.org/10.3892/ijmm.2018.3995
  • Pages: 1049-1057
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Abstract

The upregulation of long non‑coding RNA (lncRNA) human ovarian cancer‑specific transcript 2 (HOST2) has been identified in breast cancer. The present study aimed to investigate whether lncRNA HOST2 regulated the proliferation of triple negative breast cancer (TNBC) cells, and the underlying molecular mechanism. In total, 30 patients with primary TNBC, who were treated at Wuhai People's Hospital (Wuhai, China), were recruited for the present study. Reverse transcription‑quantitative polymerase chain reaction analysis was used for the examination of gene expression levels. A Cell Counting kit‑8 (CCK‑8) assay was used for the detection of cell proliferation. Phases of the cell cycle were evaluated by flow cytometry. Western blot analysis was performed to detect protein expression levels. A dual luciferase activity assay was performed to examine the interaction between microRNA (miRNA) and the 3' untranslated region (UTR) of target mRNA. The results revealed increased expression levels of HOST2 in tumor tissues from patients with TNBC. A positive correlation was identified between the expression of HOST2 and cyclin‑dependent kinase 6 (CDK6) in tumor tissues. The silencing of HOST2 induced cell proliferation inhibition and cell cycle redistribution in MDA‑MB‑231 and MDA‑MB‑468 TNBC cells. In these two cell lines, HOST2 silencing caused a decrease in the phosphorylation of RB1 and CDK6, which was observed at the mRNA and protein levels. However, the silencing of CDK6 did not alter the expression of HOST2. It was hypothesized and confirmed that let‑7b, a previously reported target miRNA of HOST2, was able to directly bind to the 3'UTR of CDK6 and repress its expression. The expression of let‑7b was negatively correlated with the expression of HOST2 and CDK6 in tumor tissues. Overall, the data suggested that lncRNA HOST2 acts as an oncogene in TNBC via the upregulation of CDK6.
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February-2019
Volume 43 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhang Y, Zhang H, Kang H, Huo W, Zhou Y and Zhang Y: Knockdown of long non-coding RNA HOST2 inhibits the proliferation of triple negative breast cancer via regulation of the let-7b/CDK6 axis. Int J Mol Med 43: 1049-1057, 2019
APA
Zhang, Y., Zhang, H., Kang, H., Huo, W., Zhou, Y., & Zhang, Y. (2019). Knockdown of long non-coding RNA HOST2 inhibits the proliferation of triple negative breast cancer via regulation of the let-7b/CDK6 axis. International Journal of Molecular Medicine, 43, 1049-1057. https://doi.org/10.3892/ijmm.2018.3995
MLA
Zhang, Y., Zhang, H., Kang, H., Huo, W., Zhou, Y., Zhang, Y."Knockdown of long non-coding RNA HOST2 inhibits the proliferation of triple negative breast cancer via regulation of the let-7b/CDK6 axis". International Journal of Molecular Medicine 43.2 (2019): 1049-1057.
Chicago
Zhang, Y., Zhang, H., Kang, H., Huo, W., Zhou, Y., Zhang, Y."Knockdown of long non-coding RNA HOST2 inhibits the proliferation of triple negative breast cancer via regulation of the let-7b/CDK6 axis". International Journal of Molecular Medicine 43, no. 2 (2019): 1049-1057. https://doi.org/10.3892/ijmm.2018.3995