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Review
. 2023 Apr 21;28(1):33.
doi: 10.1186/s11658-023-00438-9.

Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance

Mehrdad Hashemi  1   2 , Eisa Sabouni  3 , Parham Rahmanian  3 , Maliheh Entezari  1   2 , Mahsa Mojtabavi  4 , Behnaz Raei  1 , Mohammad Arad Zandieh  5 , Mitra Behroozaghdam  1 , Sepideh Mirzaei  6 , Kiavash Hushmandi  5 , Noushin Nabavi  7 , Shokooh Salimimoghadam  8 , Jun Ren  9 , Mohsen Rashidi  10   11 , Rasoul Raesi  12   13 , Afshin Taheriazam  14   15 , Athanasios Alexiou  16   17 , Marios Papadakis  18 , Shing Cheng Tan  19
Affiliations
Review

Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance

Mehrdad Hashemi et al. Cell Mol Biol Lett. .

Abstract

Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and is the most common form of liver cancer. Treatment of HCC depends on chemotherapy, radiotherapy, surgery, and immunotherapy, all of which have their own drawbacks, and patients may develop resistance to these therapies due to the aggressive behavior of HCC cells. New and effective therapies for HCC can be developed by targeting molecular signaling pathways. The expression of signal transducer and activator of transcription 3 (STAT3) in human cancer cells changes, and during cancer progression, the expression tends to increase. After induction of STAT3 signaling by growth factors and cytokines, STAT3 is phosphorylated and translocated to the nucleus to regulate cancer progression. The concept of the current review revolves around the expression and phosphorylation status of STAT3 in HCC, and studies show that the expression of STAT3 is high during the progression of HCC. This review addresses the function of STAT3 as an oncogenic factor in HCC, as STAT3 is able to prevent apoptosis and thus promote the progression of HCC. Moreover, STAT3 regulates both survival- and death-inducing autophagy in HCC and promotes cancer metastasis by inducing the epithelial-mesenchymal transition (EMT). In addition, upregulation of STAT3 is associated with the occurrence of chemoresistance and radioresistance in HCC. Specifically, non-protein-coding transcripts regulate STAT3 signaling in HCC, and their inhibition by antitumor agents may affect tumor progression. In this review, all these topics are discussed in detail to provide further insight into the role of STAT3 in tumorigenesis, treatment resistance, and pharmacological regulation of HCC.

Keywords: Hepatocellular carcinoma; Liver cancer; Molecular signaling; Noncoding transcripts; STAT3.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
A schematic representation of STAT3 in cells
Fig. 2
Fig. 2
STAT3 signaling in the regulation of apoptosis and autophagy in HCC
Fig. 3
Fig. 3
EMT mechanism regulation by STAT3 in HCC
Fig. 4
Fig. 4
STAT3 in the development of chemoresistance and radioresistance in HCC
Fig. 5
Fig. 5
Regulation of STAT3 signaling by noncoding RNAs in HCC
Fig. 6
Fig. 6
Antitumor compounds target STAT3 signaling in HCC
See this image and copyright information in PMC

References

    1. Wang X, Xiang L, Li H, Chen P, Feng Y, Zhang J, et al. The role of HMGB1 signaling pathway in the development and progression of hepatocellular carcinoma: a review. Int J Mol Sci. 2015;16(9):22527–22540. doi: 10.3390/ijms160922527. - DOI - PMC - PubMed
    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal AJ. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. doi: 10.3322/caac.21262. - DOI - PubMed
    1. Paskeh MDA, Mirzaei S, Ashrafizadeh M, Zarrabi A, Sethi GJ. Wnt/β-catenin signaling as a driver of hepatocellular carcinoma progression: an emphasis on molecular pathways. J Hepatocell Carcinoma. 2021;8:1415. doi: 10.2147/JHC.S336858. - DOI - PMC - PubMed
    1. Saalim M, Resham S, Manzoor S, Ahmad H, Jaleel S, Ashraf J, et al. IL-22: a promising candidate to inhibit viral-induced liver disease progression and hepatocellular carcinoma. Tumour Biol. 2016;37(1):105–114. doi: 10.1007/s13277-015-4294-1. - DOI - PubMed
    1. Hassan MM, Hwang L-Y, Hatten CJ, Swaim M, Li D, Abbruzzese JL, et al. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology. 2002;36(5):1206–1213. doi: 10.1053/jhep.2002.36780. - DOI - PubMed

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