Evidence map›Paper›PMID 38769521›Full record

ArticleCancer cell international2024

Smad2/3/4 complex could undergo liquid liquid phase separation and induce apoptosis through TAT in hepatocellular carcinoma.

Jiong Li, Wendi Wang, Sang Li, Zhengkang Qiao, Haoyue Jiang, Xinyue Chang, Yaning Zhu, Hongpei Tan, Xiaoqian Ma, Yuqian Dong and 12 more

Abstract read
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In one paragraph

Article in Cancer cell international, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Review
  2. [Mechanisms of RNA-binding protein phase separation in steroid-associated necrosis of the femoral head].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  3. Phase separation and the tumor microenvironment.Cell communication and signaling : CCS · 2026
    Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Machine Learning Diagnostic Model for Hepatocellular Carcinoma Based on Liquid-Liquid Phase Separation and Ferroptosis-Related Genes.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2024
    Article
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

22 authors.

Jiong LiDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Wendi WangCollege of Life Science, Liaoning University, Shenyang, China.
Sang LiEngineering and Technology Research Center for Xenotransplantation of Human Province, Changsha, China.
Zhengkang QiaoCollege of Life Science, Liaoning University, Shenyang, China.
Haoyue JiangCollege of Life Science, Liaoning University, Shenyang, China.
Xinyue ChangCollege of Life Science, Liaoning University, Shenyang, China.
Yaning ZhuDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hongpei TanDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiaoqian MaDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yuqian DongDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zhenhu HeDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zhen WangDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Qin LiuDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Shanhu YaoDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Cejun YangDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Min YangDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Lu CaoDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Juan ZhangDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Wei LiDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Wei WangDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zhe YangCollege of Life Science, Liaoning University, Shenyang, China. yangzhe@lnu.edu.cn.
Pengfei RongDepartment of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. rongpengfei66@163.com.

Funding

the Foundation of Liaoning Educational Committee of China LQN202011the Furong Scholars Programme of Hunan Province 2022the Key Research and Development Program of Hunan Province 2022SK202the National Natural Science Foundation of China 82071986The National Natural Science Foundation of China 31800688The National Natural Science Foundation of China 81971721the Science and Technology Project of Hunan Province 2021RC4017The Science and Technology Project of Hunan Province 2023JJ40882the Screening of small-molecule tumor suppression compounds project SDUZHHT〔2022〕2448the Shenyang Youth Science and Technology Innovation Project RC220177the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University 2020
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) represents one of the most significant causes of mortality due to cancer-related deaths. It has been previously reported that the TGF-β signaling pathway may be associated with tumor progression. However, the relationship between TGF-β signaling pathway and HCC remains to be further elucidated. The objective of our research was to investigate the impact of TGF-β signaling pathway on HCC progression as well as the potential regulatory mechanism involved.

methodsWe conducted a series of bioinformatics analyses to screen and filter the most relevant hub genes associated with HCC. E. coli was utilized to express recombinant protein, and the Ni-NTA column was employed for purification of the target protein. Liquid liquid phase separation (LLPS) of protein in vitro, and fluorescent recovery after photobleaching (FRAP) were utilized to verify whether the target proteins had the ability to drive force LLPS. Western blot and quantitative real-time polymerase chain reaction (qPCR) were utilized to assess gene expression levels. Transcription factor binding sites of DNA were identified by chromatin immunoprecipitation (CHIP) qPCR. Flow cytometry was employed to examine cell apoptosis. Knockdown of target genes was achieved through shRNA. Cell Counting Kit-8 (CCK-8), colony formation assays, and nude mice tumor transplantation were utilized to test cell proliferation ability in vitro and in vivo.

resultsWe found that Smad2/3/4 complex could regulate tyrosine aminotransferase (TAT) expression, and this regulation could relate to LLPS. CHIP qPCR results showed that the key targeted DNA binding site of Smad2/3/4 complex in TAT promoter region is -1032 to -1182. In addition. CCK-8, colony formation, and nude mice tumor transplantation assays showed that Smad2/3/4 complex could repress cell proliferation through TAT. Flow cytometry assay results showed that Smad2/3/4 complex could increase the apoptosis of hepatoma cells. Western blot results showed that Smad2/3/4 complex would active caspase-9 through TAT, which uncovered the mechanism of Smad2/3/4 complex inducing hepatoma cell apoptosis.

conclusionThis study proved that Smad2/3/4 complex could undergo LLPS to active TAT transcription, then active caspase-9 to induce hepatoma cell apoptosis in inhibiting HCC progress. The research further elucidate the relationship between TGF-β signaling pathway and HCC, which contributes to discover the mechanism of HCC development.

Indexed as

Caspase-9HCCLLPSSmad2/3/4 complexTAT

Identifiers

PMID38769521
PMCPMC11106862

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