MiR‐125b Loss Activated HIF1α/pAKT Loop, Leading to Transarterial Chemoembolization Resistance in Hepatocellular Carcinoma
| العنوان: | MiR‐125b Loss Activated HIF1α/pAKT Loop, Leading to Transarterial Chemoembolization Resistance in Hepatocellular Carcinoma |
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| المؤلفون: | Niya Liu, Lei Zhao, Stephanie Roessler, Fubo Ji, Xin Zheng, Zhao Ma, Junfang Ji, Xiyang Wei, Shuting Xue, Jianjuan Zhang, Ruizhe Ren, Jiong Shi, Xing Guo, Zhaogang Liu, Xin Wei Wang, Linda Wong |
| المصدر: | Hepatology |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Cohort Studies, Gene Knockout Techniques, Mice, 0302 clinical medicine, Aged, 80 and over, education.field_of_study, CD24, Liver Neoplasms, Middle Aged, Hepatocellular carcinoma, Neoplastic Stem Cells, Female, 030211 gastroenterology & hepatology, Liver cancer, Signal Transduction, medicine.drug, Adult, Carcinoma, Hepatocellular, Adolescent, Population, Transfection, Article, Young Adult, 03 medical and health sciences, Cancer stem cell, microRNA, Biomarkers, Tumor, medicine, Animals, Humans, Chemoembolization, Therapeutic, education, Aged, Hepatology, business.industry, Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, digestive system diseases, MicroRNAs, HEK293 Cells, 030104 developmental biology, HIF1A, A549 Cells, Drug Resistance, Neoplasm, Erythropoietin, Cancer research, Transcriptome, business, Proto-Oncogene Proteins c-akt |
| الوصف: | Background and aims Transarterial chemoembolization (TACE) is a standard locoregional therapy for patients with hepatocellular carcinoma (HCC) patients with a variable overall response in efficacy. We aimed to identify key molecular signatures and related pathways leading to HCC resistance to TACE, with the hope of developing effective approaches in preselecting patients with survival benefit from TACE. Approach and results Four independent HCC cohorts with 680 patients were used. MicroRNA (miRNA) transcriptome analysis in patients with HCC revealed a 41-miRNA signature related to HCC recurrence after adjuvant TACE, and miR-125b was the top reduced miRNA in patients with HCC recurrence. Consistently, patients with HCC with low miR-125b expression in tumor had significantly shorter time to recurrence following adjuvant TACE in two independent cohorts. Loss of miR-125b in HCC noticeably activated the hypoxia inducible factor 1 alpha subunit (HIF1α)/pAKT loop in vitro and in vivo. miR-125b directly attenuated HIF1α translation through binding to HIF1A internal ribosome entry site region and targeting YB-1, and blocked an autocrine HIF1α/platelet-derived growth factor β (PDGFβ)/pAKT/HIF1α loop of HIF1α translation by targeting the PDGFβ receptor. The miR-125b-loss/HIF1α axis induced the expression of CD24 and erythropoietin (EPO) and enriched a TACE-resistant CD24-positive cancer stem cell population. Consistently, patients with high CD24 or EPO in HCC had poor prognosis following adjuvant TACE therapy. Additionally, in patients with HCC having TACE as their first-line therapy, high EPO in blood before TACE was also noticeably related to poor response to TACE. Conclusions MiR-125b loss activated the HIF1α/pAKT loop, contributing to HCC resistance to TACE and the key nodes in this axis hold the potential in assisting patients with HCC to choose TACE therapy. |
| تدمد: | 1527-3350 0270-9139 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5ce8941f479b6e08e1b61631b60f15ceTest https://doi.org/10.1002/hep.31448Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5ce8941f479b6e08e1b61631b60f15ce |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15273350 02709139 |
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