Evidence map›Paper›PMID 35252056›Full record

ArticleJournal of hepatocellular carcinoma2022

MicroRNA-128-3p Mediates Lenvatinib Resistance of Hepatocellular Carcinoma Cells by Downregulating c-Met.

Xin Xu, Wenjing Jiang, Peng Han, Jingyan Zhang, Liquan Tong, Xueying Sun

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hepatocellular carcinoma, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

20 citing papers in PubMed, 36 citations in OpenAlex.

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  4. miRNAs in HCC, pathogenesis, and targets.Hepatology (Baltimore, Md.) · 2024
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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

6 authors at 1 institution in 1 country.

Xin XuHepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
Wenjing JiangHepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
Peng HanHepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
Jingyan ZhangDepartment of General Surgery, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, 163316, People's Republic of China.
Liquan TongDepartment of General Surgery, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, 163316, People's Republic of China.ORCID 0000-0002-1970-6674
Xueying SunHepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.ORCID 0000-0002-8065-8747
Harbin Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveLenvatinib is a first-line multikinase inhibitor for advanced hepatocellular carcinoma (HCC), but resistance to the drug remains a major hurdle for its long-term anti-cancer activity. This resistance is thought to be due to overexpression of c-Met. This study aims to identify potential upstream microRNAs (miRNAs) that regulate c-Met, investigate the underlying mechanisms, and seek potential strategies that may reverse such resistance.

methodsLenvatinib-resistant HCC (LR-HCC) cells were established from human HCC Huh7 and SMMC-7721 cells. Assays of cell proliferation, cell cycle distribution, apoptosis, RT-qPCR, Western blot analysis and immunohistochemistry were employed. Potential miRNAs were screened by miRNA-target prediction tools and their regulatory effects were evaluated by luciferase reporter assays. Xenograft tumor models were used to evaluate the therapeutic effects.

resultsLR-HCC cells were refractory to lenvatinib-induced growth inhibition and apoptosis in vitro and in vivo. Sustained exposure of cells to lenvatinib resulted in increased expression and phosphorylation of c-Met, and c-Met inhibition enhanced the effects of lenvatinib in suppressing LR-HCC cells. Among eleven miRNA candidates, miR-128-3p displayed the most vigorous activity to negatively regulate c-Met and was downregulated in LR-HCC cells. MiR-128-3p mimics inhibited proliferation and induced apoptosis of LR-HCC cells, and enhanced the effects of lenvatinib in cell culture and animal models. MiR-128-3p and c-Met participate in the mechanisms underlying lenvatinib resistance through regulating Akt that mediates the apoptotic pathway and ERK (extracellular-signal-regulated kinase) modulating cell cycle progression.

conclusionThe present results indicate that the miR-128-3p/c-Met axis may be potential therapeutic targets for circumventing lenvatinib resistance in HCC and warrant further investigation.

Indexed as

c-Metdrug resistancehepatocellular carcinomalenvatinibmicroRNA-128-3p

Identifiers

PMID35252056
PMCPMC8894104
OpenAlexW4214754308

What OpenQuestion holds

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Registered trials

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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.