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

Engineering 2022年第9期16卷 162-175页

作者： Tao Rui Xueyou Zhang Shi Feng Haitao Huang Shaowei Zhan Haiyang Xie Lin Zhou Shusen Zheng Qi Ling Department of Surgery Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310003China Department of Surgery Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory of Organ Transplantation Research Center for Diagnosis and Treatment of Hepatobiliary DiseasesZhejiang ProvinceHangzhou 310003China

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.

关键词： Hepatocellular carcinoma microrna cluster Exosome Multi-omics

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