The C-myc Target HnRNPAB Promotes Lung Adenocarcinoma Cell Proliferation Via Stabilization Of CDK4 MRNA

The c-Myc oncoprotein plays a prominent role in cancer initiation,progression,and maintenance.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.Increasing evidence suggests that RNA binding proteins play a critical role in the regulation of the c-Myc signaling pathway by acting as either upstream regulators or downstream effectors of c-Myc.Here we identify hnRNPAB as a new c-Myc-induced RNA binding protein.We also demonstrate that hnRNPAB is a direct transcriptional target of c-Myc.hnRNPAB belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins.Increased expression of hnRNPAB has been associated with several types of human cancers,including prostate cancer,colorectal cancer,and hepatocellular carcinoma,suggesting hnRNPAB as an oncogenic molecule.However,the function of hnRNPAB in lung adenocarcinoma remains unknown.Here,we show that hnRNPAB expression levels are elevated in lung adenocarcinoma compared with normal tissues,and elevated expression of hnRNPAB correlates with poor clinical outcome in lung adenocarcinoma patients.Besides,hnRNPAB can promote the proliferation of lung adenocarcinoma cells.These findings indicate that hnRNPAB also functions as an oncogene in lung adenocarcinoma.The subsequent functional experiments reveal that hnRNPAB promotes lung adenocarcinoma cell proliferation by accelerating G1/S cell cycle progression.Mechanistically,hnRNPAB binds to and stabilizes CDK4 mRNA,thereby increasing CDK4 expression.Moreover,hnRNPAB is able to promote G1/S cell cycle progression and cell proliferation via the regulation of CDK4.hnRNPAB is 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.