Overexpression of circular RNA hsa_circ_0001038 promotes cervical cancer cell progression by acting as a ceRNA for miR-337-3p to regulate cyclin-M3 and metastasis-associated in colon cancer 1 expression

Gene. 2020 Apr 5:733:144273. doi: 10.1016/j.gene.2019.144273. Epub 2019 Dec 3.

Abstract

Cervical cancer (CC) is a common cancer threatens women's health worldwide. Circular RNAs (circRNAs) is critically involved in carcinogenesis of various cancers. This work aimed to explore the expression pattern, functions and mechanisms of hsa_circ_0001038 in CC. RT-qPCR was performed to evaluate the levels of hsa_circ_0001038 in CC cell lines and tissues. Kaplan-Meier curves was applied to evaluate the overall survival rate of CC patients with high or low expression of hsa_circ_0001038. Fisher's exact test was analyzed to explore the relationship of hsa_circ_0001038 expression and CC patients' clinical features. Loss/Gain-of function assays were used to evaluate the role of hsa_circ_0001038 on the growth, apoptosis, migration and invasion of CC cell lines. The competing endogenous RNA (ceRNA) mechanism was predicted by bioinformatics databases and verified by dual-luciferase reporter assay. We found that hsa_circ_0001038 was highly expressed in CC cells and tissues and elevated hsa_circ_0001038 was closely related to the clinical severity including lymph node invasion and myometrial invasion. In addition, overexpressed hsa_circ_0001038 correlated with unfavorable outcome in CC patients. Knockdown of hsa_circ_0001038 attenuated cell growth, migration, and invasion but induced cell apoptosis. Ectopic expression of hsa_circ_0001038 increased cell oncogenic properties. For mechanism investigation, hsa_circ_0001038 could sponge miR-337-3p to release its suppression on cyclin-M3 (CNNM3) and metastasis-associated in colon cancer 1 (MACC1), thereby promoting CC cell growth and invasive potential, respectively. In conclusion, hsa_circ_0001038 plays an oncogenic role in CC cells partly by activating CNNM3 and MACC1.

Keywords: CNNM3; Cervical cancer; Circular RNA; Hsa_circ_0001038; MACC1; miR-337-3p.

MeSH terms

  • Adult
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • China
  • Cyclins / genetics
  • Cyclins / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • RNA / genetics
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Uterine Cervical Neoplasms / genetics*

Substances

  • CNNM3 protein, human
  • Cyclins
  • MACC1 protein, human
  • MicroRNAs
  • Mirn337 microRNA, human
  • RNA, Circular
  • Trans-Activators
  • Transcription Factors
  • RNA