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与肌管素相关的磷酸酶3促进结肠癌细胞的生长。

Myotubularin-related phosphatase 3 promotes growth of colorectal cancer cells.

作者信息

Zheng Bo'an, Yu Xiaojun, Chai Rui

机构信息

Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, China.

Department of Gastroenterological Surgery, Zhejiang Provincial People's Hospital, 158 Shangtang Road, Hangzhou, Zhejiang 310014, China.

出版信息

ScientificWorldJournal. 2014;2014:703804. doi: 10.1155/2014/703804. Epub 2014 Aug 19.

DOI:10.1155/2014/703804
PMID:25215329
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4152950/
Abstract

Due to changes in lifestyle, particularly changes in dietary habits, colorectal cancer (CRC) increased in recent years despite advances in treatment. Nearly one million new cases diagnosed worldwide and half a million deaths make CRC a leading cause of cancer mortality. In the present study, we aimed to investigate the role of myotubularin-related phosphatase 3 (MTMR3) in CRC cell growth via lentivirus-mediated small interfering RNA (siRNA) transduction in human colon cancer cell lines HCT116 and SW1116. The effect of MTMR3 knockdown on cell growth was evaluated by MTT, colony formation, and flow cytometry assays. The effect of MTMR3 knockdown on cell apoptosis was evaluated by flow cytometry with Annexin V/7-AAD double staining. The activation of apoptotic markers, Bad and PARP, was detected using Intracellular Signaling Array. Knockdown of MTMR3 resulted in a significant reduction in cell proliferation in both HCT116 and SW1116 cells. Moreover, knockdown of MTMR3 led to S phase cell cycle arrest. Furthermore, knockdown of MTMR3 induced cell apoptosis via phosphorylation of Bad and cleavage of PARP. These results indicate that MTMR3 may play an important role in the progression of CRC and suggest that siRNA mediated silencing of MTMR3 could be an effective tool in CRC treatment.

摘要

由于生活方式的改变，尤其是饮食习惯的变化，尽管治疗方法有所进步，但近年来结直肠癌（CRC）的发病率仍在上升。全球每年有近100万新诊断病例，50万人死亡，使CRC成为癌症死亡的主要原因。在本研究中，我们旨在通过慢病毒介导的小干扰RNA（siRNA）转导，在人结肠癌细胞系HCT116和SW1116中研究肌管素相关磷酸酶3（MTMR3）在CRC细胞生长中的作用。通过MTT、集落形成和流式细胞术分析评估MTMR3敲低对细胞生长的影响。通过Annexin V/7-AAD双重染色流式细胞术评估MTMR3敲低对细胞凋亡的影响。使用细胞内信号阵列检测凋亡标志物Bad和PARP的激活。MTMR3的敲低导致HCT116和SW1116细胞的细胞增殖显著降低。此外，MTMR3的敲低导致S期细胞周期停滞。此外，MTMR3的敲低通过Bad的磷酸化和PARP的裂解诱导细胞凋亡。这些结果表明，MTMR3可能在CRC的进展中起重要作用，并表明siRNA介导的MTMR3沉默可能是CRC治疗的有效工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/4152950/bb9cba39dd52/TSWJ2014-703804.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/4152950/9756ce82a191/TSWJ2014-703804.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/4152950/bac1103f04c5/TSWJ2014-703804.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/4152950/5dbb9082bd67/TSWJ2014-703804.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/4152950/bb9cba39dd52/TSWJ2014-703804.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/4152950/9756ce82a191/TSWJ2014-703804.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/4152950/bac1103f04c5/TSWJ2014-703804.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/4152950/5dbb9082bd67/TSWJ2014-703804.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/4152950/bb9cba39dd52/TSWJ2014-703804.004.jpg

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本文引用的文献

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