Epigenetic status of FBXW7 gene and its role in Ovarian cancer pathogenesis

Al Hinai, Meerah; Malgundkar, Shika Hanif; Gupta, Ishita; Lakhtakia, Ritu; Al Kalbani, Moza; Burney, Ikram; Al Moundhri, Mansour; Okamoto, Aikou; Tamimi, Yahya

doi:10.31557/APJCP.2023.24.5.1583

Epigenetic status of FBXW7 gene and its role in Ovarian cancer pathogenesis

Document Type : Research Articles

Authors

¹ Sultan Qaboos University Hospital, Oman.

² Qatar University, Qatar.

³ Department of Pathology, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE..

⁴ Department of Obstetrics and Gynecology, Sultan Qaboos University Hospital, Oman.

⁵ Sultan Qaboos Comprehensive Cancer Care and Research Centre. Muscat, Oman.

⁶ Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.

⁷ Department of Biochemistry, Sultan Qaboos University Hospital, Oman.

10.31557/APJCP.2023.24.5.1583

Abstract

Background: Chromatin immunoprecipitation (ChIP) analysis revealed that the FBXW7 gene and the long non-coding RNA (LINC01588) are potential candidates in epithelial ovarian cancer (EOC) pathogenesis. However, their exact role in EOC is not yet known. Thus, the present study sheds light on the impact of the mutations/ methylation status of the FBXW7 gene. Materials and Methods: We used public databases to assess the correlation between mutations/ methylation status and the FBXW7 expression. Furthermore, we performed Pearson’s correlation analysis between the FBXW7 gene and LINC01588. We performed gene panel exome sequencing and Methylation-speciﬁc PCR (MSP) in HOSE 6-3, MCAS, OVSAHO, and eight EOC patients’ samples to validate the bioinformatics results. Results: The FBXW7 gene was less expressed in EOC, particularly in stages III and IV, compared to healthy tissues. Furthermore, bioinformatics analysis, gene panel exome sequencing, and MSP revealed that the FBXW7 gene is neither mutated nor methylated in EOC cell lines and tissues, suggesting alternative mechanisms for FBXW7 gene regulation. Interestingly, Pearson’s correlation analysis showed an inverse, significant correlation between the FBXW7 gene and LINC01588 expression, suggesting a potential regulatory role of LINC01588. Conclusion: Neither mutations nor methylation is the causative mechanism for the FBXW7 downregulation in EOC, suggesting alternative means involving the lncRNA LINC01588.

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