Long noncoding RNA RHPN1-AS1 promotes colorectal cancer progression via targeting miR-7-5p/OGT axis

长链非编码 RNA RHPN1-AS1 通过靶向 miR-7-5p/OGT 轴促进结直肠癌进展

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作者:Wei Zheng, Hui Li, Hui Zhang, Chao Zhang, Zhonglin Zhu, Hong Liang, Yifeng Zhou

Background

Rhophilin Rho GTPase binding protein 1 antisense RNA 1 (RHPN1-AS1) is a newly discovered oncogene in several diseases, such as breast cancer, non-small cell lung cancer and uveal melanoma. Nevertheless, its molecular role in colorectal cancer (CRC) remains unknown. This paper explored the role of RHPN1-AS1 in CRC progression.

Conclusion

RHPN1-AS1 regulates CRC by mediating OGT through sponging miR-7-5p, suggesting that RHPN1-AS1 might be a potential therapeutic target for CRC.

Methods

qRT-PCR was used to detect relevant RNAs expression. CCK-8, EdU, flow cytometry, Transwell and western blot assays were performed to investigate the function of RHPN1-AS1 in CRC cells. Xenograft model was constructed to evaluate the effects of RHPN1-AS1 on tumor growth in vivo. Mechanical experiments were performed to investigate the relationship between relative genes.

Results

RHPN1-AS1 was significantly overexpressed in CRC cell lines. Knockdown of RHPN1-AS1 could inhibit cell proliferation, while stimulating cell apoptosis in vitro. Cell migration and invasion abilities were greatly suppressed after silencing RHPN1-AS1. Besides, signal transducer and activator of transcription 3 (STAT3) served as transcription factor of RHPN1-AS1. Moreover, miR-7-5p was identified as a target of RHPN1-AS1 and was negatively regulated by RHPN1-AS1 in CRC. MiR-7-5p inhibition rescued the oncogenic function of RHPN1-AS1. Additionally, O-GlcNAcylation transferase (OGT) was the downstream target of miR-7-5p. OGT overexpression could abrogate the anti-tumor effects of RHPN1-AS1 knockdown on CRC.

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