Mex-3 RNA binding family member A(MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy  

作　　者：Ri-Xin Chen Shui-Dan Xu Min-Hua Deng Shi-Hui Hao Jie-Wei Chen Xiao-Dan Ma Wei-Tao Zhuang Jing-Hua Cao Yong-Rui Lv Jin-Long Lin Si-Yu Li Gui-Bin Qiao Dan Xie Feng-Wei Wang 

机构地区：[1]Department of Thoracic Surgery,Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510080,China [2]State Key Laboratory of Oncology in South China,Guangdong Provincial Clinical Research Center for Cancer,Sun Yat-sen University Cancer Center,Guangzhou 510060,China [3]Medical Research Institute,Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510080,China [4]Department of Pathology,Sun Yat-sen University Cancer Center,Guangzhou 510060,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第5期2091-2103,共13页信号转导与靶向治疗（英文）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(No.82203715,81972227);the NSFC Incubation Project of GDPH(No.KY012021157,KY0120220052).The authors appreciate Dr.Zi-Hao Feng(Sun Yat-sen University,Guangzhou,China)for conducting bioinformatic analysis.

摘　　要：RNA-binding proteins(RBPs)-RNA networks have contributed to cancer development.Circular RNAs(circRNAs)are considered as protein recruiters;nevertheless,the patterns of circRNA-protein interactions in colorectal cancer(CRC)are still lacking.Processing bodies(PBs)formed through liquid-liquid phase separation(LLPS)are membrane-less organelles(MLOs)consisting of RBPs and RNA.Previous evidence suggests a connection between PBs dynamics and cancer progression.Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs,there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC.Herein,we identify that MEX-3 RNA binding family member A(MEX3A),frequently upregulated in CRC tissues,predicts poorer patient survival.Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells.Importantly,MEX3A undergoes intrinsically disordered regions(IDRs)-dependent LLPS in the cytoplasm.Specifically,circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins.The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A(PDE5A)mRNA degradation,consequently leading to the aggressive properties of CRC cells.Clinically,CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival.Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation,which provides prognostic markers and/or therapeutic targets for CRC.

关 键 词：COLORECTAL INHIBITING MPP 

分 类 号：R735.35[医药卫生—肿瘤]