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长链非编码 RNA RP4 通过作为 miR-7-5p 的海绵吸附作用在结直肠癌中发挥竞争性内源 RNA 的功能。

Long noncoding RNA RP4 functions as a competing endogenous RNA through miR-7-5p sponge activity in colorectal cancer.

机构信息

Department of Gastrointestinal Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, Anhui Province, China.

Department of General Surgery, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan Province, China.

出版信息

World J Gastroenterol. 2018 Mar 7;24(9):1004-1012. doi: 10.3748/wjg.v24.i9.1004.

Abstract

AIM

To investigate the role of long noncoding RNA (lncRNA) RP4 in colorectal cancer.

METHODS

Lentivirus-mediated lncRNA RP4 overexpression and knockdown were performed in the colorectal cancer cell line SW480. Cell proliferation, tumor growth, and early apoptosis were evaluated by a cell counting kit-8 assay, an xenograft tumor model, and annexin V/propidium iodide staining, respectively. Analysis of the lncRNA RP4 mechanism involved assessment of the association of its expression with miR-7-5p and the gene. Western blot analysis was also performed to assess the effect of lncRNA RP4 on the autophagy-mediated cell death pathway and phosphatidylinositol-3-kinase (PI3K)/Akt signaling.

RESULTS

Cell proliferation, tumor growth, and early apoptosis in SW480 cells were negatively regulated by lncRNA RP4. Functional experiments indicated that lncRNA RP4 directly upregulated expression by acting as a competing endogenous RNA (ceRNA) for miR-7-5p. This interaction led to activation of the autophagy-mediated cell death pathway and de-repression of PI3K and Akt phosphorylation in colorectal cancer cells .

CONCLUSION

Our results demonstrated that lncRNA RP4 is a ceRNA that plays an important role in the pathogenesis of colorectal cancer, and could be a potential therapeutic target for colorectal cancer treatment.

摘要

目的

研究长链非编码 RNA(lncRNA)RP4 在结直肠癌中的作用。

方法

在结直肠癌细胞系 SW480 中,通过慢病毒介导的 lncRNA RP4 过表达和敲低。通过细胞计数试剂盒-8 测定、异种移植肿瘤模型和 Annexin V/碘化丙啶染色分别评估细胞增殖、肿瘤生长和早期细胞凋亡。分析 lncRNA RP4 的机制包括评估其表达与 miR-7-5p 和基因的关联。还进行了 Western blot 分析,以评估 lncRNA RP4 对自噬介导的细胞死亡途径和磷脂酰肌醇-3-激酶(PI3K)/Akt 信号的影响。

结果

SW480 细胞中的细胞增殖、肿瘤生长和早期细胞凋亡受到 lncRNA RP4 的负调控。功能实验表明,lncRNA RP4 通过作为 miR-7-5p 的竞争性内源 RNA(ceRNA)直接上调表达。这种相互作用导致自噬介导的细胞死亡途径激活,并解除了结直肠癌细胞中 PI3K 和 Akt 磷酸化的抑制。

结论

我们的研究结果表明,lncRNA RP4 是一种 ceRNA,在结直肠癌的发病机制中起重要作用,可能是结直肠癌治疗的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c622/5840465/58755b4ae169/WJG-24-1004-g001.jpg

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