Long noncoding RNA HOXC-AS3 enhances the progression of cervical cancer via activating ErbB signaling pathway

• DOI: 10.1007/s10735-021-10007-z
• Publication Date: 2021-08-13T10:02:46Z
• Authors: Runsheng Zhao; Jing Song; Yiqiang Jin; Yingying Liu
• Keywords: 0301 basic medicine; Base Sequence; Carcinogenesis; Mice, Nude; Uterine Cervical Neoplasms; Middle Aged; 3. Good health; ErbB Receptors; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Disease Progression; Animals; Humans; Female; RNA, Long Noncoding; Neoplasm Metastasis; SOS1 Protein; Signal Transduction

Emerging evidence reveals that long noncoding RNAs (lncRNAs) contribute to human tumorigenesis. Nevertheless, the function of HOXC cluster antisense RNA 3 (HOXC-AS3) in human cervical cancer (CC) remains largely unknown. The levels of HOXC-AS3, miR-105-5p and SOS1 in CC tissues and cells were monitored by reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB). Gain- and loss-of-function experiments were conducted to verify the function of HOXC-AS3 and miR-105-5p in CC cells. Meanwhile, cell proliferation, apoptosis, migration and invasion were examined by the cell counting kit-8 (CCK8) experiment, colony formation assay, flow cytometry and Transwell assay. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to test the regulatory interaction of HOXC-AS3, miR-105-5p and SOS1. In addition, in vivo experiment was performed to certain the role of HOXC-AS3 in tumorigenesis of CC. HOXC-AS3 was overexpressed in CC tissues (vs. adjacent normal tissues) and CC cells. Besides, the higher HOXC-AS3 profile was associated with the poorer clinical prognosis of CC patients. Overexpression of HOXC-AS3 promoted cell growth, migration and invasion, hampered apoptosis, whereas knocking down HOXC-AS3 exhibited the reverse effects. MiR-105-5p was a downstream target of HOXC-AS3, and it mediated the HOXC-AS3-induced oncogenic effects. Mechanistically, the bioinformatic analysis illustrated that SOS1 was targeted by miR-105-5p. Up-regulating SOS1 heightened the growth, migration and invasion of CC cells by enhancing the ErbB signaling pathway, which was reversed by miR-105-5p. Up-regulated HOXC-AS3 aggravates CC by promoting SOS1 expression via targeting miR-105-5p.