LncRNA KB-1471A8.2 Overexpression Suppresses Cell Proliferation and Migration and Antagonizes the Paclitaxel Resistance of Ovarian Cancer Cells

Cancer Biother Radiopharm. 2019 Jun;34(5):316-324. doi: 10.1089/cbr.2018.2698. Epub 2019 Mar 20.

Abstract

Objective: The aim was to investigate the lncRNA KB-1471A8.2 function in ovarian cancer progression and paclitaxel resistance. Methods: The expression and distribution of KB-1471A8.2 was detected by qRT-PCR. The cell proliferation, apoptosis, invasion, migration and chemoresistance were analyzed by CCK8 assay, flow cytometry and transwell assay. The expression of DEPTOR, whose sequence is reverse overlapped with KB-1471A8.2 was analyzed by qRT-PCR, western blot and immunofluorescence. The cell cycle and the cell cycle related gene expression were analyzed by flow cytometry and qRT-PCR, respectively. Results: KB-1471A8.2 was significantly downregulated in both ovarian cancer tissues and chemoresistant ovarian cancer cells. Overexpression of KB-1471A8.2 significantly inhibited the proliferation, invasion, migration, and paclitaxel resistance, and increased the apoptosis of ovarian cancer cells. KB-1471A8.2 was mainly distributed in the nucleus of ovarian cancer cells. KB-1471A8.2 overexpression significantly decreased the S phase cell ratio, increased the G0/G1 phase cell ratio, but not affected the expression and distribution of DEPTOR. However, cyclin-dependent kinase 4 (CDK4), which is an important regulator of G1/S transition, was significantly decreased in KB-1471A8.2-overexpressed ovarian cancer cells. Conclusion: KB-1471A8.2 could significantly inhibit the development and paclitaxel resistance of ovarian cancer cells, at least partly, by suppressing CDK4 expression.

Keywords: KB-1471A8.2; migration; ovarian cancer; paclitaxel resistance; proliferation.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis
  • Cell Movement*
  • Cell Proliferation*
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / pathology
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Paclitaxel / pharmacology*
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • RNA, Long Noncoding
  • Paclitaxel