New Findings What is the central question of this study?This study was designed to investigate the molecular mechanism and biological roles of long non‐coding RNA activated by transforming growth factor‐β (lncRNA ATB) in the progression of cervical cancer. What is the main finding and its importance?Our study provided new insight into the cross‐talk between lncRNA ATB, miR‐144 and ITGA6, shedding light on the therapy for cervical cancer. Abstract The present study was designed to investigate the molecular mechanism and biological roles of long non‐coding RNA activated by transforming growth factor‐β (lncRNA ATB) in the progression of cervical cancer. The expression levels of lncRNA ATB, miR‐144 and integrin α6 (ITGA6) were detected in human cervical cancer cell lines using quantitative real‐time PCR and western blotting. Cell viability was quantified by MTT assay at 12, 24, 36, 48 and 72 h after transfection, and cell invasion was determined by the Transwell migration assay. The association among lncRNA ATB, miR‐144 and ITGA6 was disclosed by a dual‐luciferase reporter assay. We found that lncRNA ATB was highly expressed in human cervical cancer cell lines. Further investigation indicated that lncRNA ATB functioned as a competitive endogenous RNA (ceRNA) for miR‐144 to promote cervical cancer cell proliferation and invasion. We demonstrated that ITGA6 was a direct target of miR‐144, and lncRNA ATB facilitated the proliferation and invasion of cervical cancer cells via the miR‐144/ITGA5 axis. In conclusion, the lncRNA ATB/miR‐144/ITGA6 axis might be a promising therapeutic target for cervical cancer.

Vascular endothelial growth factor A (VEGFA) gene has three alternative exons which results in multiple isoforms. VEGFA has been found overexpressed in patients with endometrial cancer, but the VEGFA expression pattern and how it is regulated are still unknown. The level of VEGFA transcripts and protein isoforms were detected by semi‐quantitative Polymerase chain reaction (PCR) and immunoblotting in 29 paired endometrial tumor and adjacent nontumor control tissues. The level of three alternative splicing related proteins: RBM5, RBM6, and RBM10 was determined by immunoblotting. The H3K27Ac level in RBM10 promoter region was detected by ChIP‐PCR. The RBM10 promoter region methylation level were quantified by methylation‐sensitive high resolution melting. VEGFA165a was overexpressed and VEGFA165b level was reduced in tumors. RBM10 level was reduced in tumors. RBM10 level was negatively correlated with VEGFA165a level and positively correlated with VEGFA165b level in tumors. Using HEC‐1‐A and RL95‐2 cells, we confirmed that VEGFA165a/b expressed pattern was controlled by RBM10. MALAT1 level was increased in tumors but not involved in VEGFA alternative splicing. Reduced H3K27Ac level and increased DNA methylation in the promoter region controlled RBM10 expression in tumors. VEGFA alternative splicing in endometrial cancer was regulated by RBM10, the expression of which was controlled by histone acetylation and DNA methylation.

Although the functions of long noncoding RNA (lncRNA) called FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) have been well studied in multiple human cancer types, its expression status and detailed roles in cervical cancer remain unknown and merit investigation. This study was aimed at assessing FOXD2-AS1 expression in cervical cancer and at determining its effects on the aggressive behavior of cervical cancer in vitro and in vivo. Expression of FOXD2-AS1 in cervical cancer tissues and cell lines was determined via reverse-transcription quantitative PCR. The effects of FOXD2-AS1 on cervical cancer cells were examined by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-Htetrazolium bromide (MTT) assay, flow-cytometric analysis, migration and invasion assays, and an in vivo tumorigenicity assay. FOXD2-AS1 was found to be significantly upregulated in cervical cancer tissues and cell lines. High FOXD2-AS1 expression was notably linked with the Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and depth of cervical invasion in patients with cervical cancer. Kaplan-Meier survival analysis revealed significantly shorter overall survival of patients when the tumor expression of FOXD2-AS1 was higher in comparison with those in patients with lower FOXD2-AS1 expression. In vitro functional assays revealed that downregulation of FOXD2-AS1 led to suppression of proliferation, migration, and invasiveness as well as to the induction of apoptosis of cervical cancer cells. In addition, FOXD2-AS1 silencing hindered tumor growth in vivo. Mechanism investigation revealed that FOXD2-AS1 functioned as a molecular sponge of microRNA-760 (miR-760). Furthermore, hepatoma-derived growth factor (HDGF) was validated as a direct target gene of miR-760 in cervical cancer cells. Moreover, an miR-760 knockdown reversed the effects of FOXD2-AS1 silencing on cervical cancer cells. FOXD2-AS1 possesses significant oncogenic activity in cervical cancer progression; this activity is mediated by sponging