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Long noncoding RNA RHPN1-AS1 promotes colorectal cancer progression via targeting miR-7-5p/OGT axis.
Cancer Cell International ( IF 5.8 ) Pub Date : 2020-02-18 , DOI: 10.1186/s12935-020-1110-9
Wei Zheng 1 , Hui Li 2 , Hui Zhang 1 , Chao Zhang 1 , Zhonglin Zhu 1 , Hong Liang 1 , Yifeng Zhou 2
Affiliation  

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. 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. 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.

中文翻译:

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。

背景 Rhophilin Rho GTPase 结合蛋白 1 反义 RNA 1 (RHPN1-AS1) 是一种在乳腺癌、非小细胞肺癌和葡萄膜黑色素瘤等多种疾病中新发现的致癌基因。然而,它在结直肠癌 (CRC) 中的分子作用仍然未知。本文探讨了 RHPN1-AS1 在 CRC 进展中的作用。方法 qRT-PCR用于检测相关RNAs的表达。进行 CCK-8、EdU、流式细胞术、Transwell 和蛋白质印迹测定以研究 RHPN1-AS1 在 CRC 细胞中的功能。构建异种移植模型以评估 RHPN1-AS1 对体内肿瘤生长的影响。进行机械实验以研究相关基因之间的关系。结果 RHPN1-AS1 在 CRC 细胞系中显着过表达。敲低 RHPN1-AS1 可抑制细胞增殖,同时在体外刺激细胞凋亡。沉默 RHPN1-AS1 后,细胞迁移和侵袭能力受到极大抑制。此外,信号转导和转录激活因子 3 (STAT3) 是 RHPN1-AS1 的转录因子。此外,miR-7-5p 被鉴定为 RHPN1-AS1 的靶标,并且在 CRC 中受到 RHPN1-AS1 的负调控。MiR-7-5p 抑制挽救了 RHPN1-AS1 的致癌功能。此外,O-GlcNAcylation 转移酶 (OGT) 是 miR-7-5p 的下游靶标。OGT 过表达可以消除 RHPN1-AS1 敲低对 CRC 的抗肿瘤作用。结论 RHPN1-AS1通过海绵化miR-7-5p介导OGT调控结直肠癌,提示RHPN1-AS1可能是结直肠癌的潜在治疗靶点。沉默 RHPN1-AS1 后,细胞迁移和侵袭能力受到极大抑制。此外,信号转导和转录激活因子 3 (STAT3) 是 RHPN1-AS1 的转录因子。此外,miR-7-5p 被鉴定为 RHPN1-AS1 的靶标,并且在 CRC 中受到 RHPN1-AS1 的负调控。MiR-7-5p 抑制挽救了 RHPN1-AS1 的致癌功能。此外,O-GlcNAcylation 转移酶 (OGT) 是 miR-7-5p 的下游靶标。OGT 过表达可以消除 RHPN1-AS1 敲低对 CRC 的抗肿瘤作用。结论 RHPN1-AS1通过海绵化miR-7-5p介导OGT调控结直肠癌,提示RHPN1-AS1可能是结直肠癌的潜在治疗靶点。沉默 RHPN1-AS1 后,细胞迁移和侵袭能力受到极大抑制。此外,信号转导和转录激活因子 3 (STAT3) 是 RHPN1-AS1 的转录因子。此外,miR-7-5p 被鉴定为 RHPN1-AS1 的靶标,并且在 CRC 中受到 RHPN1-AS1 的负调控。MiR-7-5p 抑制挽救了 RHPN1-AS1 的致癌功能。此外,O-GlcNAcylation 转移酶 (OGT) 是 miR-7-5p 的下游靶标。OGT 过表达可以消除 RHPN1-AS1 敲低对 CRC 的抗肿瘤作用。结论 RHPN1-AS1通过海绵化miR-7-5p介导OGT调控结直肠癌,提示RHPN1-AS1可能是结直肠癌的潜在治疗靶点。miR-7-5p 被确定为 RHPN1-AS1 的靶标,并且在 CRC 中受到 RHPN1-AS1 的负调控。MiR-7-5p 抑制挽救了 RHPN1-AS1 的致癌功能。此外,O-GlcNAcylation 转移酶 (OGT) 是 miR-7-5p 的下游靶标。OGT 过表达可以消除 RHPN1-AS1 敲低对 CRC 的抗肿瘤作用。结论 RHPN1-AS1通过海绵化miR-7-5p介导OGT调控结直肠癌,提示RHPN1-AS1可能是结直肠癌的潜在治疗靶点。miR-7-5p 被确定为 RHPN1-AS1 的靶标,并且在 CRC 中受到 RHPN1-AS1 的负调控。MiR-7-5p 抑制挽救了 RHPN1-AS1 的致癌功能。此外,O-GlcNAcylation 转移酶 (OGT) 是 miR-7-5p 的下游靶标。OGT 过表达可以消除 RHPN1-AS1 敲低对 CRC 的抗肿瘤作用。结论 RHPN1-AS1通过海绵化miR-7-5p介导OGT调控结直肠癌,提示RHPN1-AS1可能是结直肠癌的潜在治疗靶点。
更新日期:2020-02-18
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