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微小RNA-302a通过靶向Akt在结肠癌中发挥潜在肿瘤抑制作用。

MicroRNA-302a functions as a putative tumor suppressor in colon cancer by targeting Akt.

作者信息

Sun Shengjie, Zhang Guoqing, Wu Zhiyong, Shi Weiwei, Yang Bo, Li Ying

机构信息

Department of Oncology, General Hospital of People's Liberation Army, Beijing, 100853, China.

出版信息

PLoS One. 2014 Dec 26;9(12):e115980. doi: 10.1371/journal.pone.0115980. eCollection 2014.

DOI:10.1371/journal.pone.0115980
PMID:25542007
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4277419/
Abstract

Micro RNAs (miRNAs) are important regulators involved in various physical and pathological processes, including cancer. The miRNA-302 family has been documented as playing a critical role in carcinogenesis. In this study, we investigated the role of miRNA-302a in colon cancer. MiRNA-302a expression was detected in 44 colon cancer tissues and 10 normal colon tissues, and their clinicopathological significance was analyzed. Cell proliferation and cell cycle analysis were performed on colon cancer cells that stably expressed miRNA-302a. The target gene of miRNA-302a and the downstream pathway were further investigated. Compared with normal colon tissues, miRNA-302a expression was downregulated in colon cancer tissues. Overexpression of miRNA-302a induced G1/S cell cycle arrest in colon cancer cells, and suppressed colon cancer cell proliferation both in vitro and in vivo. Furthermore, miRNA-302a inhibited AKT expression by directly binding to its 3' untranslated region, resulting in subsequent alterations of the AKT-GSK3β-cyclin D1 pathway. These results reveal miRNA-302a as a tumor suppressor in colon cancer, suggesting that miRNA-302a may be used as a potential target for therapeutic intervention in colon cancer.

摘要

微小RNA（miRNA）是参与包括癌症在内的各种生理和病理过程的重要调节因子。miRNA - 302家族已被证明在致癌过程中起关键作用。在本研究中，我们调查了miRNA - 302a在结肠癌中的作用。检测了44例结肠癌组织和10例正常结肠组织中miRNA - 302a的表达，并分析了其临床病理意义。对稳定表达miRNA - 302a的结肠癌细胞进行细胞增殖和细胞周期分析。进一步研究了miRNA - 302a的靶基因及其下游通路。与正常结肠组织相比，结肠癌组织中miRNA - 302a表达下调。miRNA - 302a的过表达诱导结肠癌细胞G1/S期细胞周期阻滞，并在体外和体内抑制结肠癌细胞增殖。此外，miRNA - 302a通过直接结合AKT的3'非翻译区抑制其表达，导致随后AKT - GSK3β - 细胞周期蛋白D1通路的改变。这些结果揭示了miRNA - 302a是结肠癌中的一种肿瘤抑制因子，表明miRNA - 302a可能作为结肠癌治疗干预的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/bc31f9354a01/pone.0115980.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/b89ee0715806/pone.0115980.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/64cf95eb4f0c/pone.0115980.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/4e8085cac71c/pone.0115980.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/5e6b1af626a2/pone.0115980.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/f2800380cb37/pone.0115980.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/bc31f9354a01/pone.0115980.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/b89ee0715806/pone.0115980.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/64cf95eb4f0c/pone.0115980.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/4e8085cac71c/pone.0115980.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/5e6b1af626a2/pone.0115980.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/f2800380cb37/pone.0115980.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/4277419/bc31f9354a01/pone.0115980.g006.jpg

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