Cervical cancer is the most common cause of female cancer‐related mortality worldwide. Decreased expression of long noncoding RNA growth arrest‐specific 5 (GAS5) is found in human cervical cancer tissues and associated with poor prognosis. However, the studies on associations between GAS5 level and malignant phenotypes, as well as sensitivity to chemotherapeutic drug in cervical cancer cells are limited. In this study, overexpression of GAS5 in cervical cancer cells resulted in prohibited cell proliferation and colony formation, which were promoted by siGAS5. Enhanced GAS5 increased cell percentage in the G0/G1 phase and decreased cells percentage in the S phase, whereas reduced expression did not. The malignant behaviors of cervical cancer cells, manifested by cell migration and invasion, could be weakened by the GAS5 overexpression and enhanced by siGAS5. Furthermore, in cisplatin‐induced cell, overexpression of GAS5 reduced cells viability and enhanced apoptosis, whereas in cells transfected with siGAS5, apoptosis eliminated. We have reported the upregulation of microRNA‐21 (miR‐21) and its oncogenetic roles in cervical cancer previously. In this study, we found the negative relationship between the GAS5 and miR‐21. Moreover, the decrease of miR‐21 associated proteins phosphorylated STAT3 and E2F3 was seen in GAS5 overexpressed cells, both of which could be increased by siGAS5. The GAS5 deficiency also reduced miR‐21 target proteins TIMP3 and PDCD4 expressions. Taken together, the GAS5 expression level is inversely associated with malignancy, but positively associated with sensitivity to cisplatin‐induced apoptosis, suggesting that GAS5 could be a biomarker of cisplatin‐resistance in clinical therapy of human cervical cancer.

Cisplatin resistance is a major challenge in cervical cancer (CC) chemotherapy. Growth arrest‐specific 5 (GAS5) has been reported to be a tumour suppressor gene in CC. However, the mechanism of GAS5 in chemoresistance remains undetermined. Our research evaluated GAS5 expression in normal and CC tissues by qPCR and in situ hybridization (ISH). Statistical analysis was conducted to analyse the association of GAS5 expression with survival. Biochemical methods were used to screen upstream and downstream regulators of GAS5. Then, interactions were confirmed by ChIP, RNA pull-down, RNA immunoprecipitation (RIP), dual-luciferase reporter and real-time PCR assays. The cisplatin sensitivity of GAS5-overexpressing CC cells was demonstrated in vitro and in vivo. The results showed that low GAS5 expression was correlated with poor overall survival. Mechanistically, GAS5 was transcriptionally modulated by P-STAT3 and served as a competing endogenous RNA (ceRNA) of miR-21 to indirectly affect cisplatin sensitivity through PDCD4 regulation in CC cells. Animal studies confirmed that GAS5 enhanced cisplatin sensitivity and promoted PDCD4 expression in vivo. GAS5 was regulated by P-STAT3 and affected the sensitivity of CC to cisplatin-based chemotherapy through the miR-21/PDCD4 axis. This result may provide new insight into cisplatin-based therapy.

A majority of cervical cancers are squamous cell carcinomas, arising from the squamous (flattened) epithelial cells that line the cervix. Long noncoding RNAs (lncRNAs) are a unique class of messenger RNA-like transcripts of at least 200 nucleotides in length with no significant protein-coding capacity. Aberrant lncRNA expression is emerging as a major component of the cancer transcriptome. In the present study, lncRNA microarrays were conducted to investigate the differentially expression lncRNAs in cervical cancer (CC) tissues compared with peritumoral tissues. Then, the most significantly upregulated lncRNA, which was lncRNA-AK001903 was selected to conduct further experiments. Real-time Quantitative polymerase chain reaction was conducted to investigate lncRNA-AK001903 expression in CC tissues and Hela, Siha, Ca Ski, C33a, H8 (HPV-immortalized cervical epithelial cell line) cell lines, and in situ hybridization histochemistry (ISHH) was performed to detect lncRNA-AK001903 expression level in different CC stages. The effect of lncRNA-AK001903 on cell proliferation, invasion and migration was assessed after knockdown of lncRNA-AK001903. The findings of the study confirmed that lncRNA-AK001903 was upregulated in CC cells and tissues compared with normal cell line H8 and peritumoral tissues. ISHH demonstrated that the expression level of lncRNA-AK001903 was connected with International Federation of Gynecology and Obstetrics (2018) stage of CC. Knockdown of lncRNA-AK001903 inhibited cell proliferation, invasion and migration in Ca Ski cells. In conclusion, lncRNA-AK001903 was demonstrated to be an oncogenic lncRNA that promotes tumor progression and may be an effective target for CC treatment in the near future.