Circ SMARCA5 Inhibited Tumor Metastasis by Interacting with SND1 and Downregulating the YWHAB Gene in Cervical Cancer

Cell Transplant. 2021 Jan-Dec:30:963689720983786. doi: 10.1177/0963689720983786.

Abstract

Cervical cancer is one of the diseases that seriously endanger women's health. Circular RNA plays an important role in regulating the occurrence and development of cervical cancer. Here, we investigated the mechanisms of circ SMARCA5 in the development of cervical cancer. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) results showed that the expression of SMARCA5 was downregulated in cervical cancer tissues and cell lines. Then we found that overexpression of SMARCA5 inhibited proliferation and invasion, but promoted apoptosis in cervical cancer cells. These were detected by Cell Counting Kit-8, Transwell, and Annexin V-fluorescein isothiocyanate/propidium iodide detection kit, respectively, and the expression of the apoptosis-related proteins was determined by western blotting. Then we predicted that SMARCA5 combined with Staphylococcal nuclease domain-containing 1 (SND1) by starBase, and verified by RNA pull-down assay. To further reveal the molecular mechanisms of SMARCA5 in the progression of cervical cancer, the interaction protein of SND1 was predicted by STRING, and the interaction was verified by co-immunoprecipitation assay. Then, the effects of SND1 or YWHAB on the development of cervical cancer were detected by the gain and loss function test, and we found that knockdown of SND1 or YWHAB reversed the effects of SMARCA5 short interfering RNA on proliferation, invasion, and apoptosis of cervical cancer cells. Overexpression of SMARCA5 inhibited cervical cancer metastasis in vivo. Our results showed that overexpression of circ SMARCA5 inhibits the binding of SND1 to YWHAB, and inhibits the proliferation and invasion, but promotes apoptosis in cervical cancer cells, thus inhibiting the metastasis of cervical cancer.

Keywords: Circ SMARCA5; SND1; YWHAB; cervical cancer; tumor metastasis.

MeSH terms

  • 14-3-3 Proteins / genetics
  • 14-3-3 Proteins / metabolism*
  • Animals
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Endonucleases / genetics
  • Endonucleases / metabolism*
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Transfection
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • 14-3-3 Proteins
  • RNA, Circular
  • YWHAB protein, human
  • Endonucleases
  • SND1 protein, human