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Sorcin promotes proliferation of hepatocellular carcinoma by regulating VEGFA/B via PI3K pathway

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Abstract

Hepatocellular carcinoma (HCC) is a highly vascularized tumor, one of the most common and lethal cancer-related tumor deaths worldwide, with cell proliferation playing a key role. In this study our western blot results and data from TAGC demonstrate a strong association between Sorcin (SRI) overexpression and poor outcomes in HCC. Moreover, SRI overexpression was remarkably effective in promoting proliferation in vitro and increasing tumor growth in vivo, which were attenuated by knocking down SRI. Mechanistically, SRI regulated vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor B (VEGFB) through PI3K/Akt/FOXO1 signal pathway. Overall, our study indicates that SRI stimulates HCC growth by controlling VEGFA/B, which presents a fresh insight into the pathogenesis of hepatocarcinogenesis and a new therapeutic target for HCC.

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Data availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

HCC:

Hepatocellular carcinoma

SRI:

Sorcin

VEGFA:

Vascular endothelial growth factor A

VEGFB:

Vascular endothelial growth factor B

VEGF:

Vascular endothelial growth factor

PI3K:

Phosphatidylinositol 3-kinase

TCGA:

The Cancer Genome Atlas

upSRI:

up-regulated SRI

shSRI:

down-regulated SRI

NC:

Negative control

PVDF:

Polyvinylidene fluoride

CCK8:

Cell Counting Kit‐8

EdU:

5-Ethynyl-2-deoxyuridine

SPF:

Specific-pathogen-free

upSRI + siVR1:

siVEGFR1 sequence was transfected into the up-regulated SRI

ACC:

Adrenocortical cancer

BLCA:

Bladder urothelial carcinoma

BRCA:

Breast invasive carcinoma

CESC:

Cervical & endocervical cancer

CHOL:

Cholangiocarcinoma

COAD:

Colon adenocarcinoma

DLBC:

Diffuse large B-cell lymphoma

ESCA:

Esophageal carcinoma

GBM:

Glioblastoma multiforme

HNSC:

Head & neck squamous cell carcinoma

KICH:

Kidney chromophobe

KIRC:

Kidney clear cell carcinoma

KIRP:

Kidney papillary cell carcinoma

LAML:

Acute myeloid leukemia

LGG:

Lower grade glioma

LIHC:

Liver hepatocellular carcinoma

LUAD:

Lung adenocarcinoma

LUSC:

Lung squamous cell carcinoma

MESO:

Mesothelioma

OV:

Ovarian serous cystadenocarcinoma

PAAD:

Pancreatic adenocarcinoma

PCPG:

Pheochromocytoma & paraganglioma

PRAD:

Prostate adenocarcinoma

READ:

Rectum adenocarcinoma

SARC:

Sarcoma

SKCM:

Skin cutaneous melanoma

STAD:

Stomach adenocarcinoma

TGCT:

Testicular germ cell tumor

THCA:

Thyroid carcinoma

THYM:

Thymoma

UCEC:

Uterine corpus endometrioid carcinoma

UCS:

Uterine carcinosarcoma

UVM:

Uveal melanoma

COAD:

Colon adenocarcinoma

READ:

Rectum adenocarcinoma

ESCA:

Esophageal carcinoma

CHOL:

Cholangiocarcinoma

PAAD:

Pancreatic adenocarcinoma

STAD:

Stomach adenocarcinoma

LIHC:

Liver hepatocellular carcinoma

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Acknowledgements

We gratefully acknowledge Key Laboratory of Tumor Metastasis of Liaoning Province. We earnestly appreciate the support of all participators. We thank the TCGA database for providing their platforms and contributing their valuable datasets.

Author information

Author notes

  1. Huan Zhang and Shanshan Hu contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China

    Huan Zhang, Shanshan Hu, Jaceline Gislaine Pires Sanches, Yizi Li & Jun Zhang

  2. Key Laboratory of Tumor Metastasis of Liaoning Province, Dalian, 116044, China

    Yuanyi Wei

  3. Dalian Public Health Clinical Center, Dalian Municipal Research Institute for Public Health, Dalian, 116031, China

    Chunwen Pu

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  1. Huan Zhang
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Contributions

Huan Zhang performed most experiments, analyzed data, and wrote original draft; Shanshan Hu performed EdU experiments; Jaceline Gislaine Pires Sanches reviewed manuscript for clarity; Yizi Li analyzed data; Yuanyi Wei took part in animal experiments; Chunwen Pu collected patients tissue samples; Jun Zhang designed experiments, and revised the manuscript; All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding authors

Correspondence to Chunwen Pu or Jun Zhang.

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Ethics approval

This study and informed consent have been examined and certified by the Ethical Committee of Dalian Public Health Clinical Center (2021–028-001) and the Ethical Committee and Institutional Review Board of Dalian Medical University (AEE20070).

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There is no competing interest.

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Key points

1. SRI promotes proliferation of HCC.

2. SRI regulates VEGFA/B in HCC.

3. PI3K/Akt/FOXO1 plays an important role during SRI promoting proliferation in HCC.

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Zhang, H., Hu, S., Sanches, J.G.P. et al. Sorcin promotes proliferation of hepatocellular carcinoma by regulating VEGFA/B via PI3K pathway. J Physiol Biochem (2024). https://doi.org/10.1007/s13105-024-01011-4

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