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Stomatin-like protein 2 promotes cell proliferation and survival under 5-Fluorouracil stress in hepatocellular carcinoma

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Abstract

Background

The crucial role of STOML2 in tumor progression has been documented recently in various cancers. Previous studies have shown that STOML2 promoted cancer cell proliferation, but the underlying mechanism is not fully illustrated.

Methods and results

The expression and clinical relevance of STOML2 in pan-cancer was analyzed by TIMER2 web platform in pan-cancer. The prognostic significance of STOML2 in HCC was evaluated utilizing KM curve and a nomogram model. Signaling pathways associated with STOML2 expression were discovered by GSEA. CCK-8 assay was performed to evaluate the proliferative capacity of HCC cells after manipulating STOML2 expression. Flow cytometry was utilized to analyze cell cycle progression. Results indicated that increased STOML2 expression in HCC linked to unfavorable clinical outcomes. Cell cycle and cell division related terms were enriched under conditions of elevated STOML2 expression via GSEA analysis. A notable decrease in cell proliferation was observed in MHCC97H with STOML2 knocked-down, accompanied by G1-phase arrest, up-regulation of p21, down-regulation of CyclinD1 and its regulatory factor MYC, while STOML2 overexpression in Huh7 showed the opposite results. These results indicated that STOML2 was responsible for HCC proliferation by regulating the expression level of MYC/cyclin D1 and p21. Furthermore, an inverse correlation was found between STOML2 expression and 5-FU sensitivity.

Conclusions

STOML2 promotes cell cycle progression in HCC which is associated with activation of MYC/CyclinD1/p21 pathway, and modulates the response of HCC to 5-FU.

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Data availability

All data accessed in this study are available on multiple publicly available databases as included within the article.

Abbreviations

HCC:

Hepatocellular carcinoma

STOML2:

Stomatin-like protein 2

TCGA:

The Cancer Genome Atlas

TIMER2:

Tumor immune estimation resource, version 2

DEGs:

Differentially expressed genes

OS:

Overall survival

GO:

Gene Ontology

BP:

Biological process

CC:

Cellular component

MF:

Molecular function

KEGG:

Kyoto Encyclopedia of Genes and Genomes

FDR:

False discovery rate

NSE:

Normalized enrichment score

qRT-PCR:

Quantitative Real-Time Polymerase Chain Reaction

NC:

Negative control

SD:

Standard deviation

5-FU:

5-Fluorouracil

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Acknowledgements

We appreciate the TCGA database, xiantao and contributors to provide their platforms and their meaningful datasets.

Funding

This work was supported by the Natural Science Foundation of China (82273420, 81972703), Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (2020RC116).

Author information

Author notes

  1. Xiaoqi Li, Yahui Zheng, Kangkang Yu and Sen Hou have contributed equally to this work.

Authors and Affiliations

  1. Department of Infectious Diseases, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China

    Xiaoqi Li, Yahui Zheng, Kangkang Yu, Ruiqi Yin, Jubo Zhang & Chong Huang

  2. Department of General Surgery, Xuchang Central Hospital, 30 Huatuo Road, Xuchang, 461001, Henan, China

    Sen Hou & Huxiao Cui

  3. Department of Infectious Disease, the Third Affiliated Hospital of Wenzhou Medical University, 108 Wansong Road, Ruian, 325207, Zhejiang, China

    Yu Zhou & Qingfeng Sun

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Contributions

CH, YZ, KY and SH designed the study, analyzed the data and prepared the manuscript; YZ and HC analyzed the data; XL and RY performed the in vitro experiment; XL, YZ, QS and CH were involved in editing and supervision. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Yu Zhou, Qingfeng Sun, Jubo Zhang or Chong Huang.

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Ethical approval was confirmed by the Huashan Hospital Research Ethics Committee.

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Supplementary Information

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11033_2023_9104_MOESM1_ESM.tif

Supplementary file1 (TIF 1696 KB)—Expression of mRNA and proteins levels of STOML2 in different cell lines. (A-B) Expression levels of STOML2 in in hepatoblastoma and HCC cells were detected by qPCR and Western blot

11033_2023_9104_MOESM2_ESM.tif

Supplementary file2 (TIF 1442 KB)—Manipulation of STOML2 expression in HCC cells and representative images of Soft agar colony formation assay. (A-D) Overexpression of STOML2 in Huh7 and knockdown in MHCC97H were detected by qRT-PCR (A-B) and Western blot (C-D). (E) Representative photographs were captured to demonstrate the impact of STOML2 overexpression on the colony formation of Huh7 cells. (F) Representative photographs were captured to illustrate the impact ofSTOML2 knockdown on the colony formation of MHCC97H cells

Supplementary file3 (DOCX 16 KB)

Supplementary file4 (DOCX 18 KB)

Supplementary file5 (DOCX 17 KB)

Supplementary file6 (DOCX 16 KB)

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Li, X., Zheng, Y., Yu, K. et al. Stomatin-like protein 2 promotes cell proliferation and survival under 5-Fluorouracil stress in hepatocellular carcinoma. Mol Biol Rep 51, 228 (2024). https://doi.org/10.1007/s11033-023-09104-x

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