ABSTRACT
Long noncoding RNAs (lncRNAs) have key functions in modulating cervical cancer (CC) genesis and progression. This work focused on exploring lncRNA HNRNPU-AS1's function in CC and the underlying mechanism. HNRNPU-AS1, AXIN2, and microRNA 205-5p (miR-205-5p) levels in CC cases were measured through reverse transcription-quantitative PCR. The relationship between miR-205-5p and AXIN2 or HNRNPU-AS1 was validated through a dual-luciferase assay. Cell proliferation was examined by CCK-8 and cell apoptosis by colony formation and flow cytometry analysis. HNRNPU-AS1 expression loss could be observed in CC patients and cell lines, which predicted the dismal prognosis of CC cases. Moreover, it was identified that the miR-205-5p level was upregulated, which acted as an inhibitory target of HNRNPU-AS1 and AXIN2. HNRNPU-AS1 inhibited cell proliferation and promoted apoptosis. As revealed by Kaplan-Meier curve, CC cases showing low HNRNPU-AS1, high miR-205-5p, and low AXIN2 levels had the poorest prognosis. AXIN2 reversed the CC cell proliferation-promoting, apoptosis-inhibiting, and Wnt/ß-catenin signaling-activating behavior mediated by miR-205-5p or HNRNPU-AS1 knockout. In conclusion, the overexpression of lncRNA HNRNPU-AS1 suppressed CC progression by inhibiting the Wnt/ß-catenin pathway through the miR-205-5p/AXIN2 axis.
Subject(s)
Axin Protein/genetics , Heterogeneous-Nuclear Ribonucleoprotein U/genetics , MicroRNAs/genetics , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Prognosis , RNA, Antisense/genetics , RNA, Long Noncoding/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/physiopathology , Wnt Signaling Pathway/genetics , beta Catenin/geneticsABSTRACT
BACKGROUND AND AIM: Relaxin is a short circulating peptide hormone. The aim of this study was to understand the role of relaxin in progression of epithelial ovarian cancer (EOC) and to assess its diagnostic and prognostic significance. METHODS: A total of 124 patients with EOC, 46 patients with benign ovarian diseases, and 50 healthy controls were recruited. Serum levels of relaxin were determined by ELISA method. The relationship between serum relaxin level and each of the clinicopathological parameters was analyzed using the χ2 test. Survival curves were plotted using the Kaplan-Meier method. The statistical difference in survival between the different groups was compared using the log-rank test. Survival correlation with the prognostic factors was further investigated by multivariate analysis using the Cox proportional hazards model with backward stepwise likelihood ratio. RESULTS: The results showed that serum relaxin level was significantly higher in patients with EOC than those with benign ovarian diseases and healthy controls (p< 0.01). Serum relaxin level was associated with FIGO stage, lymph node metastasis, tumor resectability, survival of the patients, chemotherapy and tumor recurrence (p< 0.05). Analysis using the Kaplan-meier method indicated that patients with high serum relaxin had significantly shorter overall survival time than those with low relaxin (p< 0.01). In a multivariate analysis along with clinical prognostic parameters, serum relaxin was identified as an independent adverse prognostic variable for survival. CONCLUSIONS: These results indicated that serum relaxin may be a clinically useful indicator for diagnostic and prognostic evaluation in EOC patients.
