Evidence map›Paper›PMID 32609900›Full record

ArticleHepatology (Baltimore, Md.)2021

MiR-125b Loss Activated HIF1α/pAKT Loop, Leading to Transarterial Chemoembolization Resistance in Hepatocellular Carcinoma.

Xiyang Wei, Lei Zhao, Ruizhe Ren, Fubo Ji, Shuting Xue, Jianjuan Zhang, Zhaogang Liu, Zhao Ma, Xin W Wang, Linda Wong and 6 more

Open access · greenAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.4field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 76 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 3 countries.

Xiyang Wei *MOE Key Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Lei Zhao *Shandong Cancer Hospital and Institute, Shandong Cancer Hospital of Shandong First Medical University, Jinan, China.
Ruizhe RenMOE Key Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Fubo JiMOE Key Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Shuting XueMOE Key Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Jianjuan ZhangMOE Key Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Zhaogang LiuShandong Cancer Hospital and Institute, Shandong Cancer Hospital of Shandong First Medical University, Jinan, China.
Zhao MaShandong Cancer Hospital and Institute, Shandong Cancer Hospital of Shandong First Medical University, Jinan, China.
Xin W WangLiver Cancer Program and Laboratory of Human Carcinogenesis, Cancer for Cancer Research, National Cancer Institute, Bethesda, MD.ORCID 0000-0001-9735-606X
Linda WongUniversity of Hawaii Cancer Center, Honolulu, HI.
Niya LiuMOE Key Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Jiong ShiDepartment of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Xing GuoMOE Key Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Stephanie RoesslerInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Xin ZhengEzkit LLC, Honolulu, HI.
Junfang JiMOE Key Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang University, Hangzhou, China.ORCID 0000-0002-3071-6494
Zhejiang University · CNShandong Tumor Hospital · CNHeidelberg University · DENanjing Drum Tower Hospital · CNNational Cancer Institute · USUniversity of Hawaiʻi at Mānoa · US

Funding

Strategies for improving early detection, diagnosis and treatment of liver cancerZIABC010313 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN WEI · 2009 to 2025
$18.1M
The role of cancer stem cells in liver cancer heterogeneity and subtypesZIABC010876 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN WEI · 2009 to 2025
$12.6M
Liver Cancer ProgramZIABC011870 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN WEI · 2019 to 2025
$10.1M
Molecular signatures for liver cancer diagnosis and treatment stratificationZ01BC010313 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN WEI · 1999 to 2008
$1.8M
The role of cancer stem cells in liver cancer heterogeneity and subtypesZ01BC010876 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN · 2008 to 2008
$490k
Intramural NIH HHS Z01 BC010313Intramural NIH HHS Z01 BC010876
6 · The paper itself

Abstract

BACKGROUND AND

aimsTransarterial 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

resultsFour 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.

conclusionsMiR-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.

Indexed as

A549 CellsAdolescentAdultAgedAged, 80 and overAnimalsBiomarkers, TumorCarcinoma, HepatocellularChemoembolization, TherapeuticCohort StudiesDrug Resistance, NeoplasmFemaleGene Knockout TechniquesHEK293 CellsHumansHypoxia-Inducible Factor 1, alpha SubunitBiomarkers, TumorHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMicroRNAsMIRN125 microRNA, humanProto-Oncogene Proteins c-akt

Identifiers

PMID32609900
PMCPMC9258000
OpenAlexW3038669832

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.