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Key miRNA related to TACE therapy identified for HCC patients

2020-07-12

The research team led by Prof. JI Junfang from the Zhejiang University Life Sciences Institute published a research article titled “MiR-125b Loss Activated HIF1α/pAKT Loop, Leading to Trans-Arterial Chemoembolization Resistance in Hepatocellular Carcinoma” in Hepatology on July 1, 2020. This article elaborates on the regulatory role of miRNA-125b-activated hypoxia signaling pathways in contributing to trans-arterial chemoembolization (TACE) resistance, thus providing prospective molecular signatures for TACE therapy.  

Liver cancer is the second most lethal malignant tumor among men on the worldwide basis, and approximately 80% of primary liver cancers are hepatocellular carcinomas (HCC). At present, nearly half of new HCC cases and deaths occur in China, placing the well-being of Chinese people in jeopardy. As a non-surgical palliative therapeutic technique, TACE is one of the principal adjuvant treatments after the radical resection of HCC. Although post-surgery adjuvant TACE is employed to prevent or delay the recurrence of HCC in East Asia, there is still a paucity of compelling medical evidence and it has not yet been approved by the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL). No feasible approach is clinically available for pre-selecting patients with survival benefits from TACE therapy.

In the study conducted by Prof. JI Junfang et al., researchers employed four independent HCC cohorts with 680 patients and carried out a miRNA transcriptome analysis.

This study revealed a 41‐miRNA signature related to HCC recurrence after adjuvant TACE and miR‐125b underwent the most apparent reduction in patients with HCC recurrence. Loss of miR-125b in HCC noticeably activated the HIF1α/pAKT loop in vitro and in vivo. miR‐125b directly attenuated HIF1α translation through binding to the HIF1A IRES region and targeting YB‐1, and blocked an autocrine HIF1α/PDGFβ/pAKT/HIF1α loop of HIF1α translation via targeting PDGFβ receptor. The miR‐125b‐loss/HIF1α axis induced the expression of CD24 and EPO and enriched a TACE‐resistant CD24‐positive cancer stem cell population. Patients with high CD24 or EPO in HCC had poor prognosis upon adjuvant TACE therapy. Additionally, in HCC patients having TACE as their first‐line therapy, high EPO in blood prior to TACE was also noticeably related to poor responses to TACE.