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

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Abstract

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.

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The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Conceived and designed the experiments: YJ, YL; Performed the experiments: RZ, JS; Statistical analysis: RZ, JS; Wrote the paper: RZ, JS. All authors read and approved the final manuscript.

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Correspondence to Yiqiang Jin or Yingying Liu.

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The authors declare that they have no conflict of interest.

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Our study was approved by the Medical ethics committee of Xiangyang Central Hospital.

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Zhao, R., Song, J., Jin, Y. et al. Long noncoding RNA HOXC-AS3 enhances the progression of cervical cancer via activating ErbB signaling pathway. J Mol Histol 52, 991–1006 (2021). https://doi.org/10.1007/s10735-021-10007-z

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  • DOI: https://doi.org/10.1007/s10735-021-10007-z

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