MiR-516a-3p is a Novel Mediator of Hepatocellular Carcinoma Oncogenic Activity and Cellular Metabolism

作     者：Tao Rui Xueyou Zhang Shi Feng Haitao Huang Shaowei Zhan Haiyang Xie Lin Zhou Shusen Zheng Qi Ling Tao Rui;Xueyou Zhang;Shi Feng;Haitao Huang;Shaowei Zhan;Haiyang Xie;Lin Zhou;Shusen Zheng;Qi Ling

作者机构：Department of SurgeryAffiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310003China Department of SurgeryCollaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory of Organ TransplantationResearch Center for Diagnosis and Treatment of Hepatobiliary DiseasesZhejiang ProvinceHangzhou 310003China 

出 版 物：《Engineering》 (工程（英文）)

年 卷 期：2022年第16卷第9期

页      面：162-175页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(81771713 and 81721091) the Zhejiang Provincial Natural Science Foundation of China(LR18H030001) 

主　　题：Hepatocellular carcinoma MicroRNA cluster Exosome Multi-omics 

摘      要：Hepatocellular carcinoma(HCC)remains one of the most lethal *** previously demonstrated that the chromosome 19 microRNA cluster(C19MC)was associated with tumor burden and prognosis in patients with *** the current study,we aim to explore the role of miR-516a-3p-an identical mature microRNA(miRNA)co-spliced by four oncogenic pre-miRNAs of C19MC(i.e.,mir-516a-1,mir-516a-2,mir-516b-1,and mir-516b-2)-in *** our cohort of HCC patients,miR-516a-3p was highly expressed in HCC tissues in comparison with adjacent non-tumor *** expression of tumor miR-516a-3p significantly correlated with advanced tumor stages,distinguished high HCC recurrence and mortality,and independently predicted poor *** further found that miR-516a-3p enhanced the proliferation,migration,and invasiveness of HCC cells in vitro and promoted tumor growth and metastasis in *** cancer cells,miR-516a-3p could be delivered via exosomes or extracellular vesicles and increased the oncogenic activity of recipient ***,we performed comprehensive transcriptomics,proteomics,and metabolomics analysis on the potential mechanism underlying miR-516a-3p-promoted *** DIABLO analysis showed a close correlation and strong cluster consistency between the proteomics and metabolomics *** further confirmed six proteins(i.e.,LMBR1,CHST9,RBM3,SLC7A6,PTGFRN,and NOL12)as the direct targets of miR-516a-3p and as central players in miR-516a-3p-mediated metabolism *** integrated multi-omics and co-enriched pathway analysis showed that miR-516a-3p regulates the metabolic pathways of HCC cells,particularly purine and pyrimidine *** conclusion,our findings suggest that miR-516a-3p promotes malignant behaviors in HCC cells by regulating cellular metabolism and affecting neighboring cells via the exosome delivery ***,we suggest miR-516a-3p as a novel molecular target for HCC therapy.