Article Data

  • Views 481
  • Dowloads 121

Original Research

Open Access

BRD4 inhibitor JQ1 may affect the prognosis of cervical cancer through super-enhancer-related genes

  • Yuxi Lin1,†
  • Bifen Huang2,†
  • Fangjie He3,4,*,
  • Jianqing Zheng1,5,*,

1The Second Clinical Medical College of Fujian Medical University, The Second Affiliated Hospital of Fujian Medical University, 362000 Quanzhou, Fujian, China

2Department of Obstetrics and Gynecology, Quanzhou Medical College People’s Hospital Affiliated, 362000 Quanzhou, Fujian, China

3Department of Obstetrics and Gynecology, The First People’s Hospital of Foshan, 528000 Foshan, Guangdong, China

4Department of Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 350000 Fuzhou, Fujian, China

5Department of Radiation Oncology, The Second Affiliated Hospital of Fujian Medical University, 362000 Quanzhou, Fujian, China

DOI: 10.22514/ejgo.2023.076 Vol.44,Issue 5,October 2023 pp.26-38

Submitted: 01 December 2022 Accepted: 14 February 2023

Published: 15 October 2023

*Corresponding Author(s): Fangjie He E-mail:
*Corresponding Author(s): Jianqing Zheng E-mail:

† These authors contributed equally.


To explore the effects of bromine domain protein 4 (BRD4) inhibitor JQ1 on the expression profile of super-enhancer-related genes (SE-genes) in cervical cancer (CC) HeLa cells and construct a prognosis model to explore the potential impact of JQ1 on the prognosis of CC. Whole transcriptome sequencing technology was used to detect changes in the gene expression profiles of JQ1-treated and control cells. Differentially expressed SE-genes were identified by matching via the dbCoRC database and Cistrome Data Browser (Cistrome DB). The prognosis of differentially expressed SE-genes was analyzed in the Cancer Genome Atlas (TCGA) dataset based on gene expression status. The Cox proportional risk model and least absolute shrinkage and selection operator (LASSO) regression were used to construct the prognostic model. A total of 1161 SE-genes were identified from dbCoRC and Cistrome DB, among which 1004 SE-genes were successfully matched to the expression profiles of JQ1 transcriptome sequencing. Differential expression analysis identified 110 differentially expressed SE-genes, among which 72 were down-regulated and 38 were upregulated. Then, a 9 SE-gene prognostic model was constructed, and Kaplan-Meier (K-M) curves showed that the high-risk group had significantly poorer clinical survival outcomes (p < 0.05). Time-dependent receiver operating characteristic (ROC) curves showed that the 1-year, 2-year and 3-year survival estimation of the proposed model was 0.82, 0.86 and 0.87, respectively, demonstrating excellent performance. JQ1 significantly impacts the SE-genes expression profile of HeLa cells, and the proposed model based on 9 differentially expressed SE-genes may effectively predict the survival outcomes of CC patients. As this study was based on exploratory analysis, further prospective studies are needed to verify the effectiveness of the SE-genes-based prognostic model.


BRD4 inhibitor; Cervical cancer; Super-enhancer related genes; JQ1; HeLa cells; RNA-Seq

Cite and Share

Yuxi Lin,Bifen Huang,Fangjie He,Jianqing Zheng. BRD4 inhibitor JQ1 may affect the prognosis of cervical cancer through super-enhancer-related genes. European Journal of Gynaecological Oncology. 2023. 44(5);26-38.


[1] Siegel R L, Miller K D, Fuchs H E, Jemal A. Cancer Statistics, 2021. CA: A Cancer Journal for Clinicians. 2021; 71: 7–33.

[2] Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA: A Cancer Journal for Clinicians. 2016; 66: 115–132.

[3] Yoneda JY, Teixeira JC, Derchain S, Bragança JF, Zeferino LC, Vale DB. Screen-and-treat approach in managing cervical cancer precursor lesions: an observational study with 524 women. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2023; 280: 78–82.

[4] Xie Y, Kong W, Zhao X, Zhang H, Luo D, Chen S. Immune checkpoint inhibitors in cervical cancer: current status and research progress. Frontiers in Oncology. 2022; 12: 984896.

[5] Xu Q, Wang J, Sun Y, Lin Y, Liu J, Zhuo Y, et al. Efficacy and safety of sintilimab plus anlotinib for PD-L1—positive recurrent or metastatic cervical cancer: a multicenter, single-arm, prospective phase II trial. Journal of Clinical Oncology. 2022; 40: 1795–1805.

[6] Zhang L, Mao Z, Lai Y, Wan T, Zhang K, Zhou B. A review of the research progress in T-lymphocyte immunity and cervical cancer. Translational Cancer Research. 2020; 9: 2026–2036.

[7] Parker S C, Stitzel M L, Taylor D L, Orozco JM, Erdos MR, Akiyama JA, et al. Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants. Proceedings of the National Academy of Sciences of the United States of America. 2013; 110: 17921–17926.

[8] Whyte W, Orlando D, Hnisz D, Abraham B, Lin C, Kagey M, et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell. 2013; 153: 307–319.

[9] Lovén J, Hoke H, Lin C, Lau A, Orlando D, Vakoc C, et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell. 2013; 153: 320–334.

[10] Qi T, Qu J, Tu C, Lu Q, Li G, Wang J, et al. Super-enhancer associated five-gene risk score model predicts overall survival in multiple myeloma patients. Frontiers in Cell and Developmental Biology. 2020; 8: 596777.

[11] Jiang Y, Lin D, Mayakonda A, Hazawa M, Ding L, Chien W, et al. Targeting super-enhancer-associated oncogenes in oesophageal squamous cell carcinoma. Gut. 2017; 66: 1358–1368.

[12] Liang X, Meng Y, Li C, Liu L, Wang Y, Pu L, et al. Super-enhancer-associated nine-gene prognostic score model for prediction of survival in chronic lymphocytic leukemia patients. Frontiers in Genetics. 2022; 13: 1001364.

[13] Wadhwa E, Nicolaides T. Bromodomain inhibitor review: bromodomain and extra-terminal family protein inhibitors as a potential new therapy in central nervous system tumors. Cureus. 2016; 8: e620.

[14] Li X, Duan Y, Hao Y. Identification of super enhancer-associated key genes for prognosis of germinal center B-cell type diffuse large B-cell lymphoma by integrated analysis. BMC Medical Genomics. 2021; 14: 69.

[15] Barbieri I, Cannizzaro E, Dawson MA. Bromodomains as therapeutic targets in cancer. Briefings in Functional Genomics. 2013; 12: 219–230.

[16] Noguchi-Yachide T. BET bromodomain as a target of epigenetic therapy. Chemical and Pharmaceutical Bulletin. 2016; 64: 540–547.

[17] Wang L, Xu M, Kao C, Tsai SY, Tsai M. Small molecule JQ1 promotes prostate cancer invasion via BET-independent inactivation of FOXA1. Journal of Clinical Investigation. 2020; 130: 1782–1792.

[18] Baldan F, Allegri L, Lazarevic M, Catia M, Milosevic M, Damante G, et al. Biological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cells. Journal of Oral Pathology & Medicine. 2019; 48: 214–221.

[19] Han D, Qu L, Sun L, Sun Y. Variable selection for a mark-specific additive hazards model using the adaptive LASSO. Statistical Methods in Medical Research. 2021; 30: 2017–2031.

[20] Huang M, Chen Y, Yang M, Guo A, Xu Y, Xu L, et al. DbCoRC: a database of core transcriptional regulatory circuitries modeled by H3K27ac ChIP-seq signals. Nucleic Acids Research. 2018; 46: D71–D77.

[21] Mei S, Qin Q, Wu Q, Sun H, Zheng R, Zang C, et al. Cistrome data browser: a data portal for ChIP-Seq and chromatin accessibility data in human and mouse. Nucleic Acids Research. 2017; 45: D658–D662.

[22] Thandapani P. Super-enhancers in cancer. Pharmacology & Therapeutics. 2019; 199: 129–138.

[23] Li G, Qu Q, Qi T, Teng X, Zhu H, Wang J, et al. Super-enhancers: a new frontier for epigenetic modifiers in cancer chemoresistance. Journal of Experimental & Clinical Cancer Research. 2021; 40: 174.

[24] Sengupta S, George RE. Super-enhancer-driven transcriptional dependencies in cancer. Trends in Cancer. 2017; 3: 269–281.

[25] He Y, Long W, Liu Q. Targeting super-enhancers as a therapeutic strategy for cancer treatment. Frontiers in Pharmacology. 2019; 10: 361.

[26] Liu B, Liu X, Han L, Chen X, Wu X, Wu J, et al. BRD4-directed super-enhancer organization of transcription repression programs links to chemotherapeutic efficacy in breast cancer. Proceedings of the National Academy of Sciences. 2022; 119: e2109133119.

[27] Alghamdi S, Khan I, Beeravolu N, McKee C, Thibodeau B, Wilson G, et al. BET protein inhibitor JQ1 inhibits growth and modulates WNT signaling in mesenchymal stem cells. Stem Cell Research & Therapy. 2016; 7: 22.

[28] Bagratuni T, Mavrianou N, Gavalas NG, Tzannis K, Arapinis C, Liontos M, et al. JQ1 inhibits tumour growth in combination with cisplatin and suppresses JAK/STAT signalling pathway in ovarian cancer. European Journal of Cancer. 2020; 126: 125–135.

[29] CHOI SK, HONG SH, KIM HS, SHIN CY, NAM SW, CHOI WS, et al. JQ1, an inhibitor of the epigenetic reader BRD4, suppresses the bidirectional MYC-AP4 axis via multiple mechanisms. Oncology Reports. 2016; 35: 1186–1194.

[30] Wang J, Ma X, Ma J. Identification of four enhancer-associated genes as risk signature for diffuse glioma patients. Journal of Molecular Neuroscience. 2022; 72: 410–419.

[31] Zanellato I, Colangelo D, Osella D. JQ1, a BET inhibitor, synergizes with cisplatin and induces apoptosis in highly chemoresistant malignant pleural mesothelioma cells. Current Cancer Drug Targets. 2018; 18: 816–828.

[32] Wang L, Wu X, Huang P, Lv Z, Qi Y, Wei X, et al. JQ1, a small molecule inhibitor of BRD4, suppresses cell growth and invasion in oral squamous cell carcinoma. Oncology Reports. 2016; 36: 1989–1996.

[33] Zhang Y, Duan S, Jang A, Mao L, Liu X, Huang G. JQ1, a selective inhibitor of BRD4, suppresses retinoblastoma cell growth by inducing cell cycle arrest and apoptosis. Experimental Eye Research. 2021; 202: 108304.

[34] Zhang Z, Zhang Q, Xie J, Zhong Z, Deng C. Enzyme-responsive micellar JQ1 induces enhanced BET protein inhibition and immunotherapy of malignant tumors. Biomaterials Science. 2021; 9: 6915–6926.

[35] Wang Y, Shen N, Li S, Yu H, Wang Y, Liu Z, et al. Synergistic therapy for cervical cancer by codelivery of cisplatin and JQ1 inhibiting Plk1-mutant Trp53 axis. Nano Letters. 2021; 21: 2412–2421.

[36] Rataj O, Haedicke-Jarboui J, Stubenrauch F, Iftner T. Brd4 inhibition suppresses HPV16 E6 expression and enhances chemoresponse: a potential new target in cervical cancer therapy. International Journal of Cancer. 2019; 144: 2330–2338.

[37] Kai Y, Li B E, Zhu M, Li GY, Chen F, Han Y, et al. Mapping the evolving landscape of super-enhancers during cell differentiation. Genome Biology. 2021; 22: 269.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time