MALAT1 sponges miR-106b-5p to promote the invasion and metastasis of colorectal cancer via SLAIN2 enhanced microtubules mobility
MALAT1 sponges miR-106b-5p to promote the invasion and metastasis of colorectal cancer via SLAIN2 enhanced microtubules mobility
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DOI：
10.1016/j.ebiom.2018.12.049
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发表时间：
2019-03-01
期刊：
影响因子：
11.1
通讯作者：
Wang, Xishan
中科院分区：
文献类型：
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作者：
Zhuang, Meng;Zhao, Senlin;Wang, Xishan
背景：miR93/25(miR-106b类似于25簇的成员)的低表达促进了结肠癌细胞的侵袭和转移，这预示着生存不良。然而，与25簇类似的miR-106b成员miR-106b-5p在结直肠癌中的作用尚不清楚。采用原位杂交和定量聚合酶链式反应检测MALAT1和miR-106b-5p在石蜡包埋的正常组织和结直肠癌组织中的表达。生存分析采用Kaplan-Meier分析和对数等级检验。免疫组织化学方法检测SLAIN2的表达。采用光漂白后的荧光恢复法观察微管(MT)的流动性。通过体外和体内侵袭转移实验，探讨MALAT1/miR-106b-5p/SLAIN2在大肠癌发生发展中的作用。在功能上，异位或沉默miR-106b-5p的表达抑制或促进了结直肠癌细胞的体内外侵袭和转移。长非编码区RNAMALAT1通过在体内外作为竞争的内源性RNA调节miR-106b-5p的表达，进而介导SLAIN2相关MTS的迁移，从而导致结直肠癌的进展。结论：miR-106b-5p与MALAT1/miR-106b-5p/SLAIN2共同抑制了结直肠癌患者的预后，可能是一组预测结直肠癌预后的潜在生物标志物。本研究得到了国家中国精密医学计划项目(2016YFC0905300)、中国国家自然科学基金项目(81572930)、中国科技部重点研究开发计划(2016YFC0905303、2016YFC1303200)、北京市科技攻关计划(D1710002617004)的资助。中国医学科学院非营利性中央研究院基金(2018PT32012)、中国医学科学院医学科学创新基金(CIFMS)(2016-I2M-1-001)、中国医学科学院肿瘤医院学术带头人激励基金(RC2016003)、中国肿瘤基金会北京希望跑专项基金(LC 2017A19)。上海交通大学项目(YG2017QN30)。(C)2018年由爱思唯尔出版。这是一篇CC BY-NC-ND许可证(http://creativecommons.org/licenses/by-nc-nd/4.0/).下的开放获取文章
Background: The low expression of miR93/ 25 (members of miR-106b similar to 25 cluster) promoted the invasion and metastasis of colon cancer cells, which predicted poor survival. However, the role of miR-106b-5p, the member of miR-106b similar to 25 cluster, in colorectal cancer (CRC) remains unclear.Methods: Bioinformatics methods were used to predict the potential pairs of lncRNA-miRNA-mRNA. In situ hybridization and qPCR were used to evaluate the expression of MALAT1 and miR-106b-5p in the paraffinembedded normal and CRC tissues. Kaplan-Meier analysis with the log-rank test was used for survival analyses. Immunohistochemistry stainingwas applied to investigate the expression of SLAIN2. Fluorescence recovery after photobleaching assay was applied to observe the microtubule (MT) mobility. In vitro and in vivo invasion and metastasis assays were used to explore the function of MALAT1/ miR-106b-5p/ SLAIN2 in the progression of CRC.Findings: miR-106b-5p was identified as a suppressor in CRC. Functionally, ectopic or silencing the expression of miR-106b-5p inhibited or promoted the invasion and metastasis of CRC cells in vitro and in vivo. The long noncodingRNAMALAT1 regulated themiR-106b-5p expression and further mediated themobility of SLAIN2-related MTs by functioning as a competing endogenous RNA in vitro and in vivo, which resulted in the progression of CRC. Clinically, low miR-106b-5p expression predicted poor survival of CRC patients, especially in combination with high MALAT1/ SLAIN2 expression.Interpretation: miR-106b-5p served as a suppressor in combination with MALAT1/ miR-106b-5p/ SLAIN2, which might be a group of potential prognostic biomarkers in the prognosis of CRC.Fund: This work was supported by National Program Project for Precision Medicine in National Research and Development Plan of China (2016YFC0905300), National Natural Science Foundation of China (81572930), National Key Research and Development Program of the Ministry of Science and Technology of China (2016YFC0905303, 2016YFC1303200), Beijing Science and Technology Program (D17110002617004), Non-profit Central Research Institute Fund of Chinese Academy ofMedical Sciences (2018PT32012), CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001), Incentive Fund for Academic Leaders of Oncology Hospital, Chinese Academy of Medical Sciences (RC2016003), and Beijing Hope Run Special Fund from Cancer Foundation of China (LC2017A19). The project of Shanghai Jiaotong Univversity (YG2017QN30). (c) 2018 Published by Elsevier B. V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).