RBM15通过m6A修饰调控LncRNA FGD5-AS1的稳定性参与结直肠癌细胞恶性增殖的机制

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Lin Ma , Weihua Liu , Xin Wang , Dezheng Li , Chuankui Wei
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引用次数: 0

摘要

结直肠癌(CRC)是世界上第三大常见癌症。本研究探讨了rbm15介导的m6A修饰在结直肠癌细胞恶性增殖中的作用机制。在结直肠癌细胞中检测到RBM15、LncRNA FGD5-AS1和HOXC10的表达。分析细胞内m6A水平及FGD5-AS1 RNA上m6A的富集情况。分析FGD5-AS1 RNA在结直肠癌细胞中的稳定性和定位。分析LncRNA FGD5-AS1与YBX1和YBX1与HOXC10启动子的结合。通过联合实验验证了其机理。采用裸鼠肿瘤异种移植实验验证RBM15在体内的作用机制。RBM15在结直肠癌细胞中高表达。抑制RBM15抑制结直肠癌细胞增殖,降低PCNA表达。RBM15增加了m6A对FGD5-AS1 RNA的修饰,增强了FGD5-AS1的稳定性和表达。FGD5-AS1通过将YBX1募集到HOXC10启动子中来促进HOXC10的表达。抑制YBX1抑制HOXC10的表达。FGD5-AS1或HOXC10的过表达部分逆转了RBM15抑制对结直肠癌细胞增殖的缓解作用。RBM15下调通过抑制FGD5-AS1/HOXC10轴而减弱体内CRC细胞增殖。综上所述,RBM15通过m6A修饰促进FGD5-AS1/HOXC10轴促进CRC细胞增殖。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mechanism of RBM15 in the malignant proliferation of colorectal cancer cells through regulating the stability of LncRNA FGD5-AS1 via m6A modification
Colorectal cancer (CRC) is the third most prevalent cancer all around the world. This study explored the mechanism of RBM15-mediated m6A modification in CRC cell malignant proliferation. The expression of RBM15, LncRNA FGD5-AS1, and HOXC10 was detected in CRC cells. m6A levels in cells and m6A enrichment on FGD5-AS1 RNA were analyzed. FGD5-AS1 RNA stability and localization in CRC cells were analyzed. The binding of LncRNA FGD5-AS1 to YBX1 and YBX1 to the HOXC10 promoter was analyzed. Combined experiments were conducted to validate the mechanism. Tumor xenografts in nude mice were used to verify the mechanism of RBM15 in vivo. RBM15 was highly expressed in CRC cells. RBM15 inhibition suppressed CRC cell proliferation and reduced PCNA expression. RBM15 increased m6A modification on FGD5-AS1 RNA, enhancing FGD5-AS1 stability and expression. FGD5-AS1 promoted HOXC10 expression by recruiting YBX1 to the HOXC10 promoter. YBX1 inhibition suppressed HOXC10 expression. Overexpression of FGD5-AS1 or HOXC10 partially reversed the alleviative effect of RBM15 inhibition on CRC cell proliferation. RBM15 downregulation attenuated in vivo CRC cell proliferation by inhibiting the FGD5-AS1/HOXC10 axis. In conclusion, RBM15 promotes the FGD5-AS1/HOXC10 axis via m6A modification to promote CRC cell proliferation.
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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