The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Int J Biochem Cell Biol. 2023 Mar;156:106372. doi: 10.1016/j.biocel.2023.106372. Epub 2023 Jan 16.
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.
c-Myc 癌蛋白在肿瘤发生中起着关键作用。c-Myc 的失调表达与多种人类癌症有关，包括肺腺癌。c-Myc 的致癌功能主要归因于其作为转录因子的固有性质。在这里，我们通过定量实时聚合酶链反应（qRT-PCR）、western blot、染色质免疫沉淀（ChIP）和荧光素酶报告分析报告 hnRNPAB 作为 c-Myc 的直接转录靶标。使用流式细胞术、集落形成和 RNA 免疫沉淀（RIP）分析来研究 hnRNPAB 在肺腺癌细胞增殖中的作用以及潜在的机制。hnRNPAB 通过加速 G1/S 细胞周期进程来促进肺腺癌细胞增殖，从而发挥功能。从机制上讲，hnRNPAB 与 CDK4 mRNA 相互作用并稳定其表达，从而增加 CDK4 的表达。此外，hnRNPAB 能够通过调节 CDK4 促进 G1/S 细胞周期进程和细胞增殖。hnRNPAB 还被揭示为 c-Myc 促进细胞增殖的促进作用的介导物。总之，这些发现表明 hnRNPAB 是肺腺癌细胞增殖的重要调节剂。它们还为 c-Myc 促进肿瘤发生的机制提供了新的见解。
