HTR7 and its N6-methyladenosine modification: a potential target in cell cycle regulation of cervical cancer
1Department of Gynecology, Anhui Province Maternity and Child Health Hospital, 230000 Hefei, Anhui, China
2Department of Pain Treatment, the First Affiliated Hospital of Anhui Medical University, 230000 Hefei, Anhui, China
DOI: 10.22514/ejgo.2023.020 Vol.44,Issue 2,April 2023 pp.32-41
Submitted: 29 June 2022 Accepted: 08 September 2022
Published: 15 April 2023
*Corresponding Author(s): Bin Zhang E-mail: firstname.lastname@example.org
*Corresponding Author(s): Yang Song E-mail: email@example.com
† These authors contributed equally.
Pain is highly prevalent among cancer patients. Epidemiological reports indicate that about 30%–50% of cancer patients have varying levels of pain, and about 75–95%of advanced cancer patients have chronic pain. Analgesic is the first-class choice of treatment in the final stage of cervical cancer (CC) therapeutic schedule. Early reports indicated that 5-hydroxytryptamine (5-HT) had improved pain management in cancer, while recent reports indicate that the 5-hydroxytryptamine receptor 7 (HTR7), is closely related to the occurrence and prognosis of various solid tumors. However, few articles have clarified the co-relationship between the 5-HT receptor and CC. Based on RNA-seq re-analysis, we found that HTR7 was increased in CC compared with adjacent tissues. Interestingly, Gene Set Enrichment Analysis and Kyoto encyclopedia of Genes and Genomes (GSEA-KEGG) results indicated that HTR7 could regulate CC cell cycle pathway, suggesting HTR7 as a target oncogene. Further, N6-methyladenosine (m6A) site analysis results showed that HTR7 had many m6A enzyme binding positions and YTH domain family 2 (YTHDF2), an m6A reader, was positively correlated with HTR7 in CC. Altogether, this study showed that HTR7 was elevated in human CC, affected its cell cycle, contributed to tumor procession and was regulated by the m6A enzyme, demonstrating the important mechanisms of epigenetic alteration in CC.
5-HT; HTR7; N6-methyladenosine (m6A); Cervical cancer; YTHDF2
Guo Chen,Yuting Zhu,Lu Tian,Jie Ying,Shuangyue Wu,Bin Zhang,Yang Song. HTR7 and its N6-methyladenosine modification: a potential target in cell cycle regulation of cervical cancer. European Journal of Gynaecological Oncology. 2023. 44(2);32-41.
 Hu Z, Ma D. The precision prevention and therapy of HPV-related cervical cancer: new concepts and clinical implications. Cancer Medicine. 2018; 7: 5217–5236.
 Voinea S, Herghelegiu CG, Sandru A, Ioan RG, Bohilțea RE, Bacalbașa N, et al. Impact of histological subtype on the response to chemoradiation in locally advanced cervical cancer and the possible role of surgery. Experimental and Therapeutic Medicine. 2021; 21: 93.
 Tomao F, Santangelo G, Musacchio L, Di Donato V, Fischetti M, Giancotti A, et al. Targeting cervical cancer: is there a role for poly (ADP-ribose) polymerase inhibition? Journal of Cellular Physiology. 2020; 235: 5050–5058.
 Zhang D, Zhang Y, Sun X. LINC01133 promotes the progression of cervical cancer via regulating miR-30a-5p/FOXD1. Asia-Pacific Journal of Clinical Oncology. 2021; 17: 253–263.
 Leppert W, Zajaczkowska R, Wordliczek J, Dobrogowski J, Woron J, Krzakowski M. Pathophysiology and clinical characteristics of pain in most common locations in cancer patients. Journal of Physiology and Pharmacology. 2016; 67: 787–799.
 Derry S, Wiffen PJ, Moore RA, McNicol ED, Bell RF, Carr DB, et al. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer pain in adults. The Cochrane Database of Systematic Reviews. 2017; 7: CD012638.  Liu Y, Lin B. Application of quality control circle in the treatment of moderate cancer pain in inpatients. Japanese Journal of Clinical Oncology. 2020; 50: 581–585.
 Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. The Journal of Pain. 2009; 10: 895–926.
 Chao X, Fan J, Song X, You Y, Wu H, Wu M, et al. Diagnostic strategies for recurrent cervical cancer: a cohort study. Frontiers in Oncology. 2020; 10: 591253.
 Sayers EW, Beck J, Bolton EE, Bourexis D, Brister JR, Canese K, et al. Database resources of the national center for biotechnology information. Nucleic Acids Research. 2021; 49: 10–17.
 Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Research. 2017; 45: 98–102.
 Zhou Y, Zeng P, Li YH, Zhang Z, Cui Q. SRAMP: prediction of mammalian N6-methyladenosine (m6A) sites based on sequence-derived features. Nucleic Acids Research. 2016; 44: e91.
 Wu Y, Chen Y, Li L, Yu G, Zhang Y, He Y. Associations of high-risk HPV types and viral load with cervical cancer in China. Journal of Clinical Virology. 2006; 35: 264–269.
 Dueñas-González A, Lizano M, Candelaria M, Cetina L, Arce C, Cervera E. Epigenetics of cervical cancer. An overview and therapeutic perspectives. Molecular Cancer. 2005; 4: 38.
 Saraswati W, Rosyiadi MR, Imandiri A. Electroacupuncture versus analgesics for patients with stage IIIB cervical cancer post cisplatin chemotherapy. Medical Acupuncture. 2020; 32: 293–299.
 Keszthelyi D, Troost FJ, Jonkers DM, Helyes Z, Hamer HM, Ludidi S, et al. Alterations in mucosal neuropeptides in patients with irritable bowel syndrome and ulcerative colitis in remission: a role in pain symptom generation? European Journal of Pain. 2013; 17: 1299–1306.
 Yu YB, Yang J, Zuo XL, Gao LJ, Wang P, Li YQ. Transient receptor potential vanilloid-1 (TRPV1) and ankyrin-1 (TRPA1) participate in visceral hyperalgesia in chronic water avoidance stress rat model. Neurochemical Research. 2010; 35: 797–803.
 XJ Liu, GM Wang, Y Wang, XH Niu, MY Zhang. Effect of targeted inhibition of spinal serotonergic pathway on bone cancer pain in rats. Chinese Journal of Pain Medicine. 2016; 22: 749–753.
 Wang M, Ji S, Shao G, Zhang J, Zhao K, Wang Z, et al. Effect of exosome biomarkers for diagnosis and prognosis of breast cancer patients. Clinical and Translational Oncology. 2018; 20: 906–911.
 Morita T, McClain SP, Batia LM, Pellegrino M, Wilson SR, Kienzler MA, et al. HTR7 mediates serotonergic acute and chronic itch. Neuron. 2015; 87: 124–138.
 Afzal R, Shim WS. Glucosylsphingosine activates serotonin receptor 2a and 2b: implication of a novel itch signaling pathway. Biomolecules & Therapeutics. 2017; 25: 497–503.
 Belmer A, Doly S, Setola V, Banas SM, Moutkine I, Boutourlinsky K, et al. Role of the N-terminal region in G protein-coupled receptor functions: negative modulation revealed by 5-HT2B receptor polymorphisms. Molecular Pharmacology. 2014; 85: 127–138.
 Zhang H, Herman AI, Kranzler HR, Anton RF, Zhao H, Zheng W, et al. Array-based profiling of DNA methylation changes associated with alcohol dependence. Alcoholism, Clinical and Experimental Research. 2013; 37: E108–E115.
 Wu H, Yang TY, Li Y, Ye WL, Liu F, He XS, et al. Tumor necrosis factor receptor-associated factor 6 promotes hepatocarcinogenesis by interacting with histone deacetylase 3 to enhance c-Myc gene expression and protein stability. Hepatology. 2020; 71: 148–163.
 Sun T, Wu R, Ming L. The role of m6A RNA methylation in cancer. Biomedicine & Pharmacotherapy. 2019; 112: 108613.
 Yu J, Chen M, Huang H, Zhu J, Song H, Zhu J, et al. Dynamic m6A modification regulates local translation of mRNA in axons. Nucleic Acids Research. 2018; 46: 1412–1423.
 Zhuang M, Li X, Zhu J, Zhang J, Niu F, Liang F, et al. The m6A reader YTHDF1 regulates axon guidance through translational control of Robo3.1 expression. Nucleic Acids Research. 2019; 47: 4765–4777.
 Bedi RK, Huang D, Eberle SA, Wiedmer L, Śledź P, Caflisch A. Small-molecule inhibitors of METTL3, the major human epitranscriptomic writer. ChemMedChem. 2020; 15: 744–748.
 Niu Y, Lin Z, Wan A, Chen H, Liang H, Sun L, et al. RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3. Molecular Cancer. 2019; 18: 46.
 Ni HH, Zhang L, Huang H, Dai SQ, Li J. Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer. Journal of Translational Medicine. 2020; 18: 393.
 Zhou S, Bai ZL, Xia D, Zhao ZJ, Zhao R, Wang YY, et al. FTO regulates the chemoradio therapy resistance of cervical squamouscell carcinoma (CSCC) by targeting β-catenin through mRNA demethylation. Molecular Carcinogenesis. 2018; 57: 590–597.
Vol., Issue , Invalid dateTable of contents
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.