Bioinformatic Analysis of CPEB3 in Head and Neck Squamous Cell Carcinoma via mTOR Pathway and its microRNA Targets

Y Dinesh; Karthikeyan Ramalingam; Pratibha Ramani; Selvaraj Jayaraman

doi:10.17485/IJST/v16i24.76

Article

Bioinformatic Analysis of CPEB3 in Head and Neck Squamous Cell Carcinoma via mTOR Pathway and its microRNA Targets

VIEWS 384
PDF 78

Indian Journal of Science and Technology

DOI: 10.17485/IJST/v16i24.76

Year: 2023, Volume: 16, Issue: 24, Pages: 1795-1801

Original Article

Bioinformatic Analysis of CPEB3 in Head and Neck Squamous Cell Carcinoma via mTOR Pathway and its microRNA Targets

Y Dinesh^1*, Karthikeyan Ramalingam², Pratibha Ramani², Selvaraj Jayaraman³

¹Postgraduate student, Department of Oral and Maxillofacial Pathology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India
²Professor and Head, Department of Oral and maxillofacial Pathology, Saveetha Dental College and Hospital , Saveetha Institute of Medical and Technical Sciences, Chennai, India
³Professor, Department of Biochemistry, Saveetha Dental College and Hospital , Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India

*Corresponding Author
Email: [email protected]

Received Date:11 January 2023, Accepted Date:06 May 2023, Published Date:24 June 2023

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Objectives: To analyse CPEB3 using bioinformatic tools in several types of cancer, various HNSCC cell lines based on cancer stages, tumour grades and the gene interaction, protein interaction, regulating pathway, microRNA and survival analysis. Methods: Bioinformatics tools used were UALCAN, TCGA, NCBI, GEPIA, Oncomine, cBioPortal, Human Protein Atlas, STRING, Metascape, miRNA Target Prediction Database. Findings: CPEB3 gene expression was considerably reduced in 520 HNSCC samples. Given that CPEB3 gene expression was downregulated with pathological grading grade 1 (n=62), grade 2 (n=303), grade 3 (n=125) and all 4 stages of HNSCC, this suggests that CPEB3 may be useful for determining the prognosis of HNSCC. CPEB3 gene and protein interaction revealed the high interaction with related proteins. CPEB3 expression in HNSCC causes negative regulation of cytoplasmic translation, cellular response to amino acid stimulus and downregulation of cell population proliferation. Significant low expression of CPEB3 on HNSCC patient survival p=0.013(p<0.05). CPEB3 expression was lower in HNSCC patients with an altered mTOR pathway relative to healthy controls. miRDB results showed miR- 184-5p and miR-21-5p regulate the expression of CPEB3 with corresponding target scores of 98 and 92. Novelty: This study is the first of its kind to utilise bioinformatic tools for analysis of the role of CPEB3 in several types of cancer and its related biological processes. Although there are several in silico studies on cancer, this study has involved several molecular biological processes and its impact on HNSCC. Further molecular studies based on gene knockout studies are warranted to consider CPEB3 as a potential target or a biomarker in HNSCC

Keywords: CPEB; HNSCC; mTOR; microRNA; insilico; Bioinformatics

References

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. A Cancer Journal for Clinicians. 2022;72(1):7–33. Available from: https://doi.org/10.3322/caac.21708
Sarode SC, Gondivkar S, Sarode GS, Gadbail A, Yuwanati M. Hybrid oral potentially malignant disorder: A neglected fact in oral submucous fibrosis. Oral Oncology. 2021;121:105390. Available from: https://doi.org/10.1016/j.oraloncology.2021.105390
Sridharan G, Ramani P, Patankar S, Vijayaraghavan R. Evaluation of salivary metabolomics in oral leukoplakia and oral squamous cell carcinoma. Journal of Oral Pathology & Medicine. 2019;48(4):299–306. Available from: https://doi.org/10.1111/jop.12835
Duran-Arqué B, Cañete M, Castellazzi CL, Bartomeu A, Ferrer-Caelles A, Reina O, et al. Comparative analyses of vertebrate CPEB proteins define two subfamilies with coordinated yet distinct functions in post-transcriptional gene regulation. Genome Biology. 2022;23(1). Available from: https://doi.org/10.1186/s13059-022-02759-y
Mingo DRD, Pantoja-Uceda D, Hervás R, Carrión-Vázquez M, Laurents DV. Conformational dynamics in the disordered region of human CPEB3 linked to memory consolidation. BMC Biology. 2022;20(1):129. Available from: https://doi.org/10.1186/s12915-022-01310-6
Ivshina MP, Spijker HMV&, Jung S, Ponny SR, Schafer DP, Richter JD. CPEB1 regulates the inflammatory immune response, phagocytosis, and alternative polyadenylation in microglia. Glia. 2022;70(10):1850–1863. Available from: https://doi.org/10.1002/glia.24222
Wang G, Ji X, Li PX, Wang W. Human bone marrow mesenchymal stem cell-derived exosomes containing microRNA-425 promote migration, invasion and lung metastasis by down-regulating CPEB1. Regenerative Therapy. 2022;20:107–116. Available from: https://doi.org/10.1016/j.reth.2022.03.007
Zeng W, Yue L, Lam KSW, Zhang W, So WKK, Tse EHY, et al. CPEB1 directs muscle stem cell activation by reprogramming the translational landscape. Nature Communications. 2022;13(1):947. Available from: https://doi.org/10.1038/s41467-022-28612-1
Kozlov E, Shidlovskii YV, Gilmutdinov R, Schedl P, Zhukova M. The role of CPEB family proteins in the nervous system function in the norm and pathology. Cell & Bioscience. 2021;11(1). Available from: https://doi.org/10.1186/s13578-021-00577-6
Chen J, Li L, Liu TYY, Fu HFF, Lai YHH, Lei X, et al. CPEB3 suppresses gastric cancer progression by inhibiting ADAR1-mediated RNA editing via localizing ADAR1 mRNA to P bodies. Oncogene. 2022;41(41):4591–4605. Available from: https://doi.org/10.1038/s41388-022-02454-z
Wang H, Peng D, Gan M, He Z, Kuang Y. CPEB3 overexpression caused by miR-106b-5p inhibition inhibits esophageal carcinoma in-vitro progression and metastasis. Anti-Cancer Drugs. 2022;33(4):335–351. Available from: https://doi.org/10.1097/CAD.0000000000001265
Jeevanandan G, Thomas E. Volumetric analysis of hand, reciprocating and rotary instrumentation techniques in primary molars using spiral computed tomography: An in vitro comparative study. European Journal of Dentistry. 2018;12(01):021–026. Available from: https://doi.org/10.4103/ejd.ejd_247_17
Ponnulakshmi R, Shyamaladevi B, Vijayalakshmi P, Selvaraj J. In silico and in vivo analysis to identify the antidiabetic activity of beta sitosterol in adipose tissue of high fat diet and sucrose induced type-2 diabetic experimental rats. Toxicology Mechanisms and Methods. 2019;29(4):276–290. Available from: https://doi.org/10.1080/15376516.2018.1545815
Skubal M, Gielen GH, Waha A, Gessi M, Kaczmarczyk L, Seifert G, et al. Altered splicing leads to reduced activation of CPEB3 in high-grade gliomas. Oncotarget. 2106;7(27):41898–41912. Available from: https://doi.org/10.18632/oncotarget.9735
Tang H, Han X, Feng Y, Hao Y. linc00968 inhibits the tumorigenesis and metastasis of lung adenocarcinoma via serving as a ceRNA against miR-9-5p and increasing CPEB3. Aging. 2020;12(22):22582–22598. Available from: https://doi.org/10.18632/aging.103833
Fang Y, Zhong Q, Wang Y, Gu C, Liu S, Li A, et al. CPEB3 functions as a tumor suppressor in colorectal cancer via JAK/STAT signaling. Aging. 2020;12(21):21404–21422. Available from: https://doi.org/10.18632/aging.103893
Zhong Q, Fang Y, Lai Q, Wang S, He C, Li A, et al. CPEB3 inhibits epithelial-mesenchymal transition by disrupting the crosstalk between colorectal cancer cells and tumor-associated macrophages via IL-6R/STAT3 signaling. Journal of Experimental & Clinical Cancer Research. 2020;39(1):132. Available from: https://doi.org/10.1186/s13046-020-01637-4
Alsawalha M, Rao CV, Al-Subaie AM, Haque SM, Veeraraghavan VP, Surapaneni KM. Novel mathematical modelling of Saudi Arabian natural diatomite clay. Materials Research Express. 2019;6(10):105531. Available from: http://dx.doi.org/10.1088/2053-1591/ab2f9b
Shree KH, Shree H, Ramani K, P, Sherlin H, Sukumaran G, et al. Saliva as a Diagnostic Tool in Oral Squamous Cell Carcinoma - a Systematic Review with Meta Analysis. Pathology & Oncology Research. 2019;25:447–453. Available from: http://dx.doi.org/10.1007/s12253-019-00588-2
Hannah RH, Ramani R, Ramanathan P, Jancy A, Gheena MR, S. CYP2 C9 polymorphism among patients with oral squamous cell carcinoma and its role in altering the metabolism of benzo[a]pyrene. 2020. Available from: http://dx.doi.org/10.1016/j.oooo.2020.06.021

Copyright

© 2023 Dinesh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Published By Indian Society for Education and Environment (iSee)