HNRNPU-AS1 Regulates Cell Proliferation and Apoptosis via the MicroRNA 205-5p/AXIN2 Axis and Wnt/β-Catenin Signaling Pathway in Cervical Cancer

• Published in: Molecular and cellular biology 2021-09, Vol.41 (10), p.e0011521-e0011521
• Main Authors: Niu, Zhaoyuan, Wang, Fengling, Lv, Shihui, Lv, Yingpin, Liu, Ming, Fu, Lei, Yao, Yushuang, Wang, Lingzhi, Lin, Wei, Yuan, Fang
• Format: Article
• Language: English
• Subjects: apoptosis; Apoptosis - genetics; Axin Protein - genetics; AXIN2; beta Catenin - genetics; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; cervical cancer; Female; Gene Expression - genetics; Gene Expression Regulation, Neoplastic - genetics; Heterogeneous-Nuclear Ribonucleoprotein U - genetics; HNRNPU-AS1; Humans; MicroRNAs - genetics; miR-205-5p; Molecular and Cellular Biology; Prognosis; proliferation; Research Article; RNA, Antisense - genetics; RNA, Long Noncoding - genetics; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - physiopathology; Wnt Signaling Pathway - genetics; Wnt/β-catenin
• ISSN: 0270-7306; 1098-5549; 1098-5549
• DOI: 10.1128/MCB.00115-21

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/β-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/β-catenin pathway through the miR-205-5p/AXIN2 axis.