The c-Myc targeting hnRNPAB promotes lung adenocarcinoma cell proliferation via stabilization of CDK4 mRNA.
The c-Myc targeting hnRNPAB promotes lung adenocarcinoma cell proliferation via stabilization of CDK4 mRNA.
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DOI：
10.1016/j.biocel.2023.106372
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发表时间：
2023-01
期刊：
影响因子：
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通讯作者：
Chenglai Xu;Bingyan Li;N. Yu;Bo Yao;Fang Wang;Yide Mei
中科院分区：
文献类型：
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作者：
Chenglai Xu;Bingyan Li;N. Yu;Bo Yao;Fang Wang;Yide Mei
c-Myc癌蛋白在肿瘤发生中起关键作用。c-Myc表达失调与包括肺腺癌在内的多种人类癌症有关。c-Myc的致癌功能在很大程度上归因于其作为转录因子的内在性质。在这里，我们报告的RNA结合蛋白hnRNPAB作为一个直接的转录靶点的c-Myc进行定量实时聚合酶链反应（qRT-PCR），蛋白质印迹，染色质免疫沉淀（ChIP），和荧光素酶报告分析。流式细胞术，集落形成，RNA免疫沉淀（RIP）分析被用来研究hnRNPAB在肺腺癌细胞增殖中的作用，以及潜在的机制。HnRNPAB在功能上显示通过加速G1/S细胞周期进程来促进肺腺癌细胞增殖。在机制上，hnRNPAB与CDK 4 mRNA相互作用并稳定CDK 4 mRNA，从而增加CDK 4表达。此外，hnRNPAB还能通过调控CDK 4的表达，促进G1/S期细胞的增殖。HnRNPAB也被揭示为c-Myc对细胞增殖的促进作用的介导剂。总之，这些发现表明hnRNPAB是肺腺癌细胞增殖的重要调节因子。他们还为c-Myc如何促进肿瘤发生的机制提供了新的见解。
The c-Myc oncoprotein plays a pivotal role in tumorigenesis. The deregulated expression of c-Myc has been linked to a variety of human cancers including lung adenocarcinoma. The oncogenic function of c-Myc has been largely attributed to its intrinsic nature as a transcription factor. Here we reported the RNA binding protein hnRNPAB as a direct transcriptional target of c-Myc by performing quantitative real-time polymerase chain reaction (qRT-PCR), western blot, chromatin immunoprecipitation (ChIP), and luciferase reporter analyses. Flow cytometry, colony formation, and RNA immunoprecipitation (RIP) assays were used to investigate the role of hnRNPAB in lung adenocarcinoma cell proliferation, as well as the underlying mechanism. HnRNPAB was functionally shown to promote lung adenocarcinoma cell proliferation by accelerating G1/S cell cycle progression. Mechanistically, hnRNPAB interacted with and stabilized CDK4 mRNA, thereby increasing CDK4 expression. Moreover, hnRNPAB was able to promote G1/S cell cycle progression and cell proliferation via the regulation of CDK4. HnRNPAB was also revealed as a mediator of the promoting effect of c-Myc on cell proliferation. Together, these findings demonstrate that hnRNPAB is an important regulator of lung adenocarcinoma cell proliferation. They also add new insights into the mechanisms of how c-Myc promotes tumorigenesis.