Evidence map›Paper›PMID 33771969›Full record

ArticleCell death & disease2021

MIRLET7BHG promotes hepatocellular carcinoma progression by activating hepatic stellate cells through exosomal SMO to trigger Hedgehog pathway.

Yunhong Xia, Lu Zhen, Hongxia Li, Shuomin Wang, Sun Chen, Chongchong Wang, Xiaoyu Yang

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.3field-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

30 citing papers in PubMed, 45 citations in OpenAlex.

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  7. Current issues in molecular biology · 2025
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  16. [Hepatocellular Carcinoma-Derived Exosomes: Key Players in Intercellular Communication Within the Tumor Microenvironment].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024
    Article
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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

7 authors at 3 institutions in 1 country.

Yunhong Xia *Department of Oncology, the Fourth Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, China. yhxia12@sina.com.
Lu Zhen *Department of General Surgery, the Fourth Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, China.
Hongxia Li *Department of Oncology, Hefei First People's Hospital, Anhui Medical University, Hefei, 230022, China.
Shuomin WangDepartment of Oncology, the Fourth Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, China.
Sun ChenDepartment of Oncology, the Fourth Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, China.
Chongchong WangDepartment of Oncology, the Fourth Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, China.
Xiaoyu YangDepartment of Oncology, the Fourth Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, China.
Anhui Medical University · CNFourth Affiliated Hospital of Anhui Medical University · CNHefei First People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC), commonly caused by liver fibrosis, is a global challenge with high morbidity. Activation of hepatic stellate cells (HSCs) contributes to hepatic fibrosis. Exosomes are small vesicles that play a significant role in cell-to-cell communication. Smoothened (SMO) is the key signal transducer for Hedgehog pathway. This study was designed to study the function and underlying mechanism of SMO in HSC activation. Functional assays including 5-Ethynyl-2´-deoxyuridine, colony formation, wound healing, transwell, and sphere formation assays disclosed the function of SMO. Western blot analysis of exosome biomarkers, immunofluorescence staining assay, electron microscope, and flow cytometry revealed the existence of exosomes. Bioinformatics analyses and mechanistic assays uncovered the interplays between RNAs. Nude mice xenograft model was established to evaluate HCC tumor growth. We uncovered that SMO was an oncogene in HCC cells and was low-expressed in quiescent HSCs. Then, SMO was upregulated in HSCs cultured with HCC cells-conditioned medium. Next, it was revealed that HCC cells-derived exosomes activated HSCs by transmitting SMO to HSCs. Subsequently, we recognized that microRNA let-7b host gene (MIRLET7BHG) served as the competing endogenous RNA against miR-330-5p to upregulate SMO. In turn, SMO induced hedgehog pathway to promote GLI family zinc finger 1 (Gli1), leading to transcriptional activation of MIRLET7BHG in activated HSCs. In summary, this study demonstrated that Gli1-induced MIRLET7BHG facilitated HCC by activating HSCs through exosomal SMO to stimulate hedgehog pathway, providing a new road for HCC treatment.

Indexed as

AnimalsCarcinoma, HepatocellularCell Line, TumorDisease ProgressionExosomesHedgehog ProteinsHepatic Stellate CellsHeterograftsHumansLiver NeoplasmsMaleMiceMice, NudeMicroRNAsNeoplastic Stem CellsSmoothened ReceptorHedgehog ProteinsMicroRNAsmirnlet7 microRNA, humanSmoothened ReceptorSMO protein, human

Identifiers

PMID33771969
PMCPMC7997896
OpenAlexW3138500547

What OpenQuestion holds

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LicenceCC BY
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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.