Long non-coding RNA TPT1-AS1 sensitizes breast cancer cell to paclitaxel and inhibits cell proliferation by miR-3156-5p/caspase 2 axis

Hum Cell. 2021 Jul;34(4):1244-1254. doi: 10.1007/s13577-021-00541-z. Epub 2021 May 17.

Abstract

Long non-coding RNAs (lncRNAs) are key modulators during cancer progression. Application of using lncRNA expression to evaluate patient prognosis and sensitivity to treatment is highly anticipated, yet the expression and mechanism of many lncRNAs remain unknown. Herein, we projected for the investigation of TPT1-AS1 function in breast cancer. TPT1-AS1 was assessed by bioinformatic analysis of publicly available datasets and quantitative real-time PCR (qRT-PCR). Cell sensitivity to paclitaxel and cell proliferation was measured by flow cytometry and CCK-8. Interaction among TPT1-AS1, microRNA (miRNA, miR)-3156-5p and Caspase 2 (CASP2) was studied by bioinformatic analysis, qRT-PCR, western blot as well as dual luciferase reporter assay. Herein, TPT1-AS1 was significantly diminished in breast cancer from publicly available datasets and our collected samples. In breast cancer cells, TPT1-AS1 overexpression repressed cell proliferation and sensitized breast cancer cells to paclitaxel. RegRNA 2.0 predicted a potential interaction between TPT1-AS1 and miR-3156-5p which was confirmed by qRT-PCR as well as dual luciferase reporter assay. CASP2, a proapoptotic gene, was corroborated to be targeted by miR-3156-5p. Meanwhile, TPT1-AS1 upregulated CASP2 in breast cancer cells, and its biological function was reversed by CASP2 knockdown. Collectively, TPT1-AS1 diminished cell proliferation and sensitized cells to chemotherapy by sponging miR-3156-5p and upregulating CASP2, acting as a biomarker for patients with breast cancer.

Keywords: Breast cancer; CASP2; Cell proliferation; Paclitaxel sensitivity; TPT1-AS1.

MeSH terms

  • Antineoplastic Agents, Phytogenic* / pharmacology
  • Biomarkers, Tumor* / metabolism
  • Biomarkers, Tumor* / physiology
  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Caspase 2 / metabolism
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Humans
  • MicroRNAs* / metabolism
  • Paclitaxel / pharmacology
  • RNA, Antisense*
  • RNA, Long Noncoding* / physiology
  • Tumor Cells, Cultured
  • Tumor Protein, Translationally-Controlled 1
  • Up-Regulation / genetics

Substances

  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • Caspase 2
  • MicroRNAs
  • Paclitaxel
  • RNA, Long Noncoding
  • TPT1 protein, human
  • Tumor Protein, Translationally-Controlled 1
  • RNA, Antisense