Evidence map›Paper›PMID 35642354›Full record

ArticleCancer science2023

SREBF2-STARD4 axis confers sorafenib resistance in hepatocellular carcinoma by regulating mitochondrial cholesterol homeostasis.

Xuetian Yue, Youzi Kong, Yankun Zhang, Min Sun, Shuyue Liu, Zhuanchang Wu, Lifen Gao, Xiaohong Liang, Chunhong Ma

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

Article in Cancer science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.8field-weighted citation impact, top 7% 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

24 citing papers in PubMed, 34 citations in OpenAlex.

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  18. METTL3 and METTL14-mediated NScientific reports · 2024
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  19. Review
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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

9 authors at 1 institution in 1 country.

Xuetian YueDepartment of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.ORCID https://orcid.org/0000-0001-5561-4964
Youzi KongDepartment of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Yankun ZhangKey Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province, and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College of Medicine, Shandong University, Jinan, China.
Min SunDepartment of Hernia and Abdominal Wall Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Shuyue LiuDepartment of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Zhuanchang WuKey Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province, and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College of Medicine, Shandong University, Jinan, China.
Lifen GaoKey Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province, and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College of Medicine, Shandong University, Jinan, China.
Xiaohong LiangKey Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province, and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College of Medicine, Shandong University, Jinan, China.
Chunhong MaKey Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province, and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College of Medicine, Shandong University, Jinan, China.
Shandong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sorafenib resistance limits its survival benefit for treatment of hepatocellular carcinoma (HCC). Cholesterol metabolism is dysregulated in HCC, and its role in sorafenib resistance of HCC has not been fully elucidated. Aiming to elucidate this, in vitro and in vivo sorafenib resistant models were established. Sterol regulatory element binding transcription factor 2 (SREBF2), the key regulator of cholesterol metabolism, was activated in sorafenib resistant HepG2 and Huh7 cells. Knockdown of SREBF2 resensitized sorafenib resistant cells and xenografts tumors to sorafenib. Further study showed that SREBF2 positively correlated with StAR related lipid transfer domain containing 4 (STARD4) in our sorafenib resistant models and publicly available datasets. STARD4, mediating cholesterol trafficking, not only promoted proliferation and migration of HepG2 and Huh7 cells, but also increased sorafenib resistance in liver cancer. Mechanically, SREBF2 promoted expression of STARD4 by directly binding to its promoter region, leading to increased mitochondrial cholesterol levels and inhibition of mitochondrial cytochrome c release. Importantly, knockdown of SREBF2 or STARD4 decreased mitochondrial cholesterol levels and increased mitochondrial cytochrome c release, respectively. Moreover, overexpression of STARD4 reversed the effect of SREBF2 knockdown on mitochondrial cytochrome c release and sorafenib resistance. In conclusion, SREBF2 promotes STARD4 transcription, which in turn contributes to mitochondrial cholesterol transport and sorafenib resistance in HCC. Therefore, targeting the SREBF2-STARD4 axis would be beneficial to a subset of HCC patients with sorafenib resistance.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsCarrier ProteinsCell Line, TumorCell ProliferationCholesterolCytochromes cDrug Resistance, NeoplasmHomeostasisHumansMembrane Transport ProteinsSorafenibSterol Regulatory Element Binding Protein 2Carrier ProteinsCholesterolCytochromes cMembrane Transport ProteinsSorafenibSREBF2 protein, humanSTARD4 protein, humanSterol Regulatory Element Binding Protein 2cholesterol transportmitochondrial membrane permeabilitysorafenib resistanceSREBF2StAR

Identifiers

PMID35642354
PMCPMC9899602
OpenAlexW4281752757

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.