Dataset Information

MiR-423-5p target identification with proteomics in HCC

ABSTRACT: Hepatocellular carcinoma (HCC) remains a significant clinical challenge due to limited diagnostic and therapeutic options. Non-coding RNAs, such as microRNAs (miRNAs), play key roles in cancer biology. Our previous findings showed that miR-423-5p exerts anti-cancer effects on HCC patients treated with sorafenib by promoting autophagy. In this study, we investigated the molecular mechanisms underlying its activity by generating SNU-387 HCC cell line stably overexpressing miR-423-5p and conducting a comprehensive proteomic analysis. Mass spectrometry profiling identified 698 differentially expressed proteins (DEPs) in miR-423-5p-overexpressing cells compared to controls. Functional enrichment analysis revealed significant alterations in metabolic pathways, particularly purine/pyrimidine metabolism and gluconeogenesis. To relate these findings to clinical context, we integrated experimentally validated and predicted miR-423-5p targets with The Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma (LIHC) dataset. Seven candidate proteins were significantly associated with patient prognosis (log-rank p < 0.05 for both overall and disease-free survival). These targets were downregulated in our miR-423-5p model but found to be upregulated in stage III HCC tissues from TCGA data.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Hepatocellular Carcinoma

SUBMITTER: David Boocock

LAB HEAD: David Boocock

PROVIDER: PXD064869 | Pride | 2025-09-29

REPOSITORIES: pride

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Dataset's files

Source:

			Action	DRS
	201209_Amalia_Mir_pLKO_report.pg_matrix.tsv	Tabular
	201209_Mir1.wiff	Wiff
	201209_Mir1.wiff.scan	Wiff
	201209_Mir2.wiff	Wiff
	201209_Mir2.wiff.scan	Wiff

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Publications

Proteomic profiling identifies miR-423-5p as a modulator of oncogenic metabolism in HCC.

Luce Amalia A Bocchetti Marco M Cossu Alessia Maria AM Tathode Madhura S MS Boocock David J DJ Coveney Clare C Romano Maria Preziosa MP De Iesu Maria Roberta MR Simeone Ines I Mele Luigi L Vitale Giovanni G Sperlongano Rossella R Misso Gabriella G Verderio Elisabetta A M EAM Zappavigna Silvia S Caraglia Michele M

Journal of translational medicine 20250924 1

<h4>Background</h4>Hepatocellular carcinoma (HCC) remains a significant clinical challenge due to limited diagnostic and therapeutic options. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), play key roles in cancer biology. Our previous findings showed that miR-423-5p enhances anti-cancer effects on HCC patients treated with sorafenib by promoting autophagy. Here, we investigated the molecular mechanisms underlying miR-423-5p function through a comprehensive proteomic approach.<h4>Methods< ...[more]

PMID: 40993657

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Project description:MicroRNAs (miRNAs) are abundant in the circulation and play a central role in diverse biological processes; they may be useful for early diagnosis of hepatocellular carcinoma (HCC). We conducted a two-phase, case-control study (20 pairs for the discovery set and 49 pairs for the validation set) to test the hypothesis that genome-wide dysregulation of circulating miRNAs differentiate HCC cases from controls. Taqman low density arrays were used to examine genome-wide miRNA expression for the discovery set, and quantitative RT-PCR was used to validate candidate miRNAs for both discovery and validation sets. Sixty-six miRNAs were found to be significantly over-expressed in plasma of HCC cases compared to controls after adjusting for false discovery rate (p<0.05). A volcano plot indicated that 7 miRNAs had greater than 2-fold case-control differences with p<0.01. Four significant miRNAs (miR-150, miR-30c, miR-483-5p and miR-520b) detectable in all samples with varied expression levels were further validated in a validation set. MiR-483-5p was statistically significantly over-expressed in HCC cases compared with controls (3.20 vs. 0.82, p<0.0001). HCC risk factors and clinic-pathological characteristics did not influence miR-483-5p expression. The combination of plasma miR-483-5p level and HCV status can significantly differentiate HCC cases from controls with an AUC of 0.908 (p<0.0001). The sensitivity and specificity were, respectively, 75.5% and 89.8%. These preliminary results suggest the importance of dysregulated circulating miR-483-5p as a potential HCC biomarker. Confirmation of aberrant expression of miR-483-5p in a large prospective HCC study will provide support for its application to HCC detection. A hospital-based HCC case-control study including 20 HCC patients and 20 controls is conducted in Columbia University Medical Center (CUMC), which is approved by the Institutional Review Board. Cases were newly diagnosed HCC patients who were treated in the Hepatobiliary Oncology Clinics, CUMC, and examined pathologically. Controls were recruited from volunteers through the Research Recruitment and Minority Outreach (RRMO) core of Herbert Irving Comprehensive Cancer Center (HICCC). Flyers were placed at strategic locations around CUMC where hospital visitors and employees frequent or were handed out at inreach events at the hospital or at outreach events in the community. Interested participants were directed to contact the trained recruitment staff from the RRMO and given further information about participation. Interested participants were excluded from the control group if diagnosed for any kind of cancer or liver disease. Eligible controls were asked to fill out the same demographic and epidemiological questionnaire as HCC cases. In the current study, controls were matched with HCC cases on age (M-BM-15 yrs), gender (male/female) and ethnicities (Caucasian/Hispanic/African-American/Asian).