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.

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

Background: Cervical cancer (CC) ranks as the second most common malignancy in women, accounting for more two 2 million deaths every year in the world. Recently, circular RNAs (circRNAs) have been reported to regulate the progression of multiple human tumors; however, whether it involves in CC remains largely elusive. Materials and Methods: Two GEO circRNA expression profiles (GSE102686, GSE113696) were downloaded to analyze the differentially expressed circRNAs using bioinformatics methods. Expression of circ_103973, miR-335 and PPP6C in CC tissues and cell lines were examined by qRT-PCR. Cell apoptosis was assessed with PI/Annexin-V double staining followed by the analysis of flow cytometry. Cell proliferation was evaluated by MTT and colony formation assays. Interaction between circ_103973 and miR-335, as well as miR-335 and PPP6C, were verified by dual-luciferase reporter assay. Results: Circ_103973 was found to be highly expressed in both GSE102686 and GSE113696 datasets as well as in CC tissue samples and cell lines. Higher levels of circ_103973 were correlated to a worse outcome of CC patients. Knockdown of circ_103973 significantly promoted CC cell apoptosis and inhibited CC cell proliferation in vitro. Mechanistically, we demonstrated that circ_103973 served as a sponge of miR-335, which directly targeted PPP6C in CC cells. miR-335 was found to be decreased in CC, while PPP6C was found to be increased in CC. Moreover, anti-miR-335 could reverse the inhibitory effects of circ_103973 knockdown on CC cell proliferation, and this phenomenon could be blocked by si-PPP6C. Conclusion: Circ_103973 promoted CC cell proliferation in vitro by physically binding miR-335, which further targeted and regulated PPP6C.

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