LncRNA-FGD5-AS1 promotes 5-Fu resistance of cervical cancer cells through modulating the miR-130a-3p-YTHDF2 axis.

Abstract

Cervical cancer is one of the most common gynecologic malignancies worldwide. 5-Fluorouracil (5-Fu) is a widely used anticancer drug for various cancers, but the development of 5-Fu resistance poses a challenge in treating cervical cancer patients. This study examined the roles and molecular mechanisms of LncRNA-FGD5-AS1 in 5-Fu resistant cervical cancer cells through in vitro and in vivo experiments. We discovered FGD5-AS1 and the RNA methylation reader protein, YTHDF2, were positively associated with 5-Fu resistance in cervical cancer. A positive correlation between FGD5-AS1 and YTHDF2 was found in cervical tumor tissues. Expressions of FGD5-AS1 and YTHDF2 were significantly upregulated in the established 5-Fu resistant cervical cancer cells. MiRNA-microArray analysis screened that FGD5-AS1 downregulated miR-130a-3p expression in cervical cancer cells. Subsequently, we demonstrated FGD5-AS1 acted as a ceRNA by sponging miR-130a-3p, which targeted the 3'UTR of YTHDF2 mRNA. Rescue experiments validated overexpression of FGD5-AS1 increased 5-Fu resistance in cervical cancer cells, which was reversed by miR-130a-3p overexpression. Finally, combining FGD5-AS1 silencing with 5-Fu treatments resulted in a synergistic inhibitory effect (CI < 1) on the viability of cervical cancer cells. This study reveals a FGD5-AS1-miR-130a-3p-YTHDF2 axis that could be a promising therapeutic target for overcoming 5-Fu resistance in cervical cancer.