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SOX2 regulates radioresistance in cervical cancer via the hedgehog signaling pathway
Abstract
Objective Resistance to radiotherapy accounts for most treatment failures in cervical cancer patients who receive radical radiation therapy. To discover the possible mechanism of radioresistance and improve the 5-year survival rate, we focused on how sex-determining region Y-box 2 (SOX2) mediates radioresistance in cervical cancer as well as on the interaction between SOX2 and the hedgehog (Hh) signaling pathway in this study. Methods We established the acquired radioresistant subclone cells Hela-RR and Siha-RR. RT-qPCR, Western blot analysis, IHC, clonogenic survival assay, CCK-8 assay, apoptosis analysis, cell cycle analysis and xenograft models were used to explore the relationship between SOX2 expression and radiation resistance and to determine how SOX2 mediates radioresistance in cervical cancer. Furthermore, luciferase reporter and ChIP-PCR assays were utilized to assess the interaction between SOX2 and the Hh signaling pathway. Results Our research suggested that high expression of SOX2 was responsible for radioresistance in cervical cancer. SOX2 was observed to be closely related to irradiation-induced survival, proliferation, apoptosis, and cell cycle changes. The Hh signaling pathway was found to be activated in Hela-RR and Siha-RR, and the activation changed with SOX2 expression. IHC staining of SOX2 and Gli1 showed a close relationship between SOX2 and the Hh pathway. Luciferase reporter and ChIP-PCR assays demonstrated that SOX2 interacted with the Hh signaling pathway by occupying the HHAT promoter. Conclusions SOX2 is a potential therapeutic target of irradiation resistance in cervical cancer. It mediates radioresistance in cervical cancer via the Hh signaling pathway.
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“Nevertheless, the efficacy of DNA damaging-based therapies is limited by toxicities and the acquisition of therapy resistance [3], particularly associated with a suboptimal regression during radiotherapy of CC patients [4].”
From Combining Mitomycin C with inhibition of BAD phosphorylation enhances apoptotic cell death in advanced cervical cancer (2024) · cites this paper as [3]
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Metadata
- Authors
- Huang, C., Lu, H., Li, J., Xie, X., Fan, L., Wang, D., Tan, W., Wang, Y., Lin, Z., & Yao, T.
- Affiliations
- Sun Yat-sen University (CN)
- First Affiliated Hospital of Xiamen University (CN)
- Corresponding author
- Lin, Zhongqiu
- Yao, Tingting
- ORCID
- Venue
- Gynecologic Oncology
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 151
- Issue
- 3
- Pages
- 533-541
- ISSN
- 0090-8258 (ISSN-L)
- OpenAlex
- W2896784508
- Cited by
- 51
- References
- 38
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 17 · 2020: 10 · 2019: 2
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gynecologic Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81572575, 81602290)
- Guangdong Province Natural Scientific Grant (2014A030313109, 2016A020215059)
- Science and Technology Planning Project of Guangzhou (201601020102)
- Guangdong College Students' Innovation and Entrepreneurship Training Program (1055813194)
- National College Students' Innovation and Entrepreneurship Training Program (201310558097)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Keywords
- SOX2, radioresistance (biology), cervical cancer, Hedgehog signaling, Gli1, apoptosis, cell cycle, therapeutic target
- MeSH terms
- Animals, Uterine Cervical Neoplasms, Female, Humans, Mice, Nude, Middle Aged, Signal Transduction, Hedgehog Proteins, SOXB1 Transcription Factors
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