STAT3/HOTAIR Signaling Axis Regulates HNSCC Growth in an EZH2-dependent Manner
Published version of a preprint
Abstract
Purpose: PI3K and STAT3 are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate head and neck squamous cell cancer (HNSCC) growth. The lncRNA HOX transcript antisense RNA (HOTAIR) was found to modulate the progression of HNSCC. In this study, we attempted to establish the correlation of PI3K/STAT3/HOTAIR signaling with the progression of HNSCC and its sensitivity toward platinum-based and targeted anti-EGFR combination therapy. Experimental Design: We first analyzed the STAT3/HOTAIR and PI3K/AKT level in human HNSCC samples. We then activated or suppressed STAT3/HOTAIR and determined the effects on HNSCC cell proliferation in vitro and the growth of UM1 xenograft tumor, an orthotopic model of HNSCC. The sensitivity of HNSCC cells toward cisplatin and cetuximab was determined by in vitro assays. Results: HNSCC samples showed significantly robust expression/activation of STAT3, HOTAIR, PI3K, and AKT, compared with normal squamous epithelium. STAT3 inhibition with WP1066 decreased HOTAIR level and sensitized HNSCC to cisplatin or cetuximab. STAT3 promoted HOTAIR transcription and its interaction with pEZH2-S21, resulting in enhanced growth of HNSCC cells. In addition, overexpression of HOTAIR promoted the growth of UM1 xenograft tumors in vivo. Conclusions: Our results suggest that STAT3 signaling promotes HNSCC progression via regulating HOTAIR and pEZH2-S21 in HNSCC with PI3K overexpression/activation. These findings provide a rationale to target the STAT3/HOTAIR/pEZH2-S21 regulatory axis for treating patients with HNSCC. Clin Cancer Res; 24(11); 2665–77. ©2018 AACR.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The STAT3/HOTAIR/EZH2 axis may serve as a novel therapeutic target for combination therapy of cisplatin and cetuximab to treat patients with HNSCC with PI3K activation.
“Moreover, X. Zhou proved that the STAT3/HOTAIR/EZH2 axis may serve as a novel therapeutic target for combination therapy of cisplatin and cetuximab to treat patients with HNSCC with PI3K activation (58).”
From Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer (2022) · cites this paper as [58]
The citation lists haven’t been fetched yet
References 60 · Cited by 93
- Authors
- Sun, S., Wu, Y., Guo, W., Yu, F., Kong, L., Ren, Y., Wang, Y., Yao, X., Jing, C., Zhang, C., Liu, M., Zhang, Y., Zhao, M., Li, Z., Wu, C., Qiao, Y., Yang, J., Wang, X., Zhang, L., Li, M., & Zhou, X.
- Affiliations
- Tianjin Medical University Cancer Institute and Hospital (CN)
- 3Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, National Clinical Research Center of Cancer, Tianjin, China.
- Tianjin Medical University General Hospital (CN)
- Tianjin Medical University (CN)
- University of Oklahoma Health Sciences Center (US)
- Corresponding author
- Zhang, Lun
- Li, Min
- Zhou, Xuan
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2018-05-31
- Volume
- 24
- Issue
- 11
- Pages
- 2665-2677
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2793372930
- Cited by
- 93
- References
- 60
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 11 · 2023: 11 · 2022: 11 · 2021: 24 · 2020: 9 · 2019: 15 · 2018: 4
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (NSFC) (NSFC81572492, NSFC81702529)
- National Clinical Research Center for Cancer (Not provided)
- Special Program of Talents Development for Excellent Youth Scholars in Tianjin (Not provided)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- STAT3, HOTAIR, EZH2, head and neck squamous cell carcinoma, PI3K/Akt signaling, long non-coding RNA, cisplatin sensitivity, cetuximab, EGFR, combination therapy, tumor growth, WP1066
- MeSH terms
- Enhancer of Zeste Homolog 2 Protein, Squamous Cell Carcinoma of Head and Neck, Animals, Antineoplastic Agents, Cell Cycle, Disease Models, Animal, Humans, Signal Transduction, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, Xenograft Model Antitumor Assays, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Cell Proliferation, STAT3 Transcription Factor, Mice, RNA, Long Noncoding
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
