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

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.