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长非编码 RNA RP11-400N13.3 通过调控 miR-4722-3p/P2RY8 轴促进结直肠癌的进展。

Long non‑coding RNA RP11‑400N13.3 promotes the progression of colorectal cancer by regulating the miR‑4722‑3p/P2RY8 axis.

机构信息

Department of Geriatric Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.

Transfusion Medicine Research Department, Yunnan Kunming Blood Center, Kunming, Yunnan 650106, P.R. China.

出版信息

Oncol Rep. 2020 Nov;44(5):2045-2055. doi: 10.3892/or.2020.7755. Epub 2020 Sep 7.

DOI:10.3892/or.2020.7755
PMID:32901883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7551293/
Abstract

Accumulating evidence has shown that long non‑coding RNAs (lncRNAs) play significant roles in the development and progression of many types of cancer including colorectal cancer. RP11‑400N13.3 is a novel lncRNA discovered recently and its biological function and underlying mechanism in colorectal cancer remain elusive. This study aimed to reveal the relationship between RP11‑400N13.3 and colorectal cancer. Our results demonstrated that the expression of RP11‑400N13.3 was significantly upregulated in both colorectal cancer tissues and cell lines as compared to normal adjacent tissues and normal colonic epithelial cells by RT‑qPCR, respectively. Upregulation of RP11‑400N13.3 was found to be correlated with a poor overall survival rate. Functional studies revealed that RP11‑400N13.3 facilitated the proliferation, migration, invasion and tumor growth of colorectal cancer cells while inhibiting the apoptosis of cancer cells in vitro and in vivo. We also observed that RP11‑400N13.3 serves as a sponge for miR‑4722‑3p, and that P2Y receptor family member 8 (P2RY8) was predicted to be a target of miR‑4722‑3p by bioinformatics analysis. Western blot assay indicated that the expression of P2RY8 was negatively or positively regulated by miR‑4722‑3p or RP11‑400N13.3. In addition, rescue experiments revealed that RP11‑400N13.3 promoted proliferation, migration and invasion by directly regulating the expression of miR‑4722‑3p and P2RY8. In conclusion, our results revealed that RP11‑400N13.3 promoted colorectal cancer progression via modulating the miR‑4722‑3p/P2RY8 axis, thus suggesting RP11‑400N13.3 as a potential therapeutic target for the treatment of colorectal cancer.

摘要

越来越多的证据表明,长非编码 RNA(lncRNA)在包括结直肠癌在内的许多类型癌症的发生和发展中发挥重要作用。RP11-400N13.3 是最近发现的一种新型 lncRNA,其在结直肠癌中的生物学功能和潜在机制尚不清楚。本研究旨在揭示 RP11-400N13.3 与结直肠癌的关系。我们的研究结果表明,通过 RT-qPCR,RP11-400N13.3 在结直肠癌组织和细胞系中的表达明显高于正常相邻组织和正常结肠上皮细胞。RP11-400N13.3 的上调与总生存率降低相关。功能研究表明,RP11-400N13.3 促进结直肠癌细胞的增殖、迁移、侵袭和肿瘤生长,同时抑制癌细胞的凋亡。我们还观察到,RP11-400N13.3 作为 miR-4722-3p 的海绵,通过生物信息学分析预测 P2Y 受体家族成员 8(P2RY8)是 miR-4722-3p 的靶标。Western blot 检测表明,P2RY8 的表达受 miR-4722-3p 或 RP11-400N13.3 的负调控或正调控。此外,挽救实验表明,RP11-400N13.3 通过直接调节 miR-4722-3p 和 P2RY8 的表达来促进增殖、迁移和侵袭。总之,我们的研究结果表明,RP11-400N13.3 通过调节 miR-4722-3p/P2RY8 轴促进结直肠癌的进展,提示 RP11-400N13.3 可能成为治疗结直肠癌的潜在治疗靶点。

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