Abstract 1496: Circulating mir21 and mir125b in women living with human immunodeficiency virus: Utility of biomarkers for monitoring cervical carcinogenesis

Abstract

Background: As of 2018, the prevalence of Human immunodeficiency virus (HIV), and cervical cancer (Ca) attributable to HIV was higher in Africa than in other continents. Identifying individuals at a high risk of developing Ca among immunocompromised persons, using less invasive techniques, remains a major challenge. Purpose: The study evaluated HIV infection-associated dysregulation of Ca-linked oncomirs (miR-21, miR-146a, miR-155, miR-182, and miR-200c) and tumor suppressors (miR-let-7b, miR-125b, miR-143, miR-145, and p53 gene), in a bid to identify early indicators of genetic instability, and biomarkers for monitoring of high-risk individuals. Methods: This case-control study included 173 women without abnormal Pap smear; confirmed HIV seropositive women (HIV+ = 103) and HIV seronegative women (HIV- = 70). Relative expressions of miRNAs and p53 gene in blood and cervical cells) were determined following RNA extraction, reverse transcriptase Polymerase Chain Reaction (PCR), and gel electrophoresis. T-test was used to compare the data from HIV+ and HIV- women. Significance was set at p≤ 0.05. Results: Similar pattern of miR-21, miR-146a, miR-182, miR-200c, miR-125b, and miR-145 expression was observed in both samples. Higher expressions of miR-155 and p53 gene were observed in cervical cells of HIV+ women compared with HIV- women (p= 0.046, and 0.033, respectively) whereas lower expressions of miR-155 and p53 gene were observed in the blood of HIV+ women compared with HIV- women (p= 0.539 and 0.049, respectively). In both blood and cervical cells, higher miR-21 expression (p= 0.032 and 0.198, respectively) and lower miR-125b expression (p= 0.050 and 0.004, respectively) were observed in HIV+ women compared with HIV-women. In blood, a lower expression of miR-146a was observed in HIV+ women compared with HIV- women (p= 0.036) whereas in cervical cells, lower expressions of miR-182 and miR-200c were observed in HIV+ women compared with HIV- women (p= 0.035 and 0.045, respectively). The low expression of miR-146a, miR-182, and miR-200c in HIV+ women could be due to immune exhaustion, viral immune evasive mechanism, or an indicator of viral latency while the higher expression of miR-21, and lower expression of miR-125b and p53 could be early indicators of genetic instability prior to epithelial transformation. Conclusion: This study suggests that circulating high expression of miR-21 and low expression of miR-125b and p53 gene could be used in identifying individuals at risk of developing Ca, especially among immunocompromised patients. Keywords: Human immunodeficiency virus, Cervical cancer, Detection, Biomarkers, MicroRNAs Citation Format: Jude Ogechukwu Okoye, Anthony Ajuluchukwu Ngokere, Charles Chinedum Onyenekwe, Samuel Ifedioranma Ogenyi, Olaposi Omotuyi. Circulating mir21 and mir125b in women living with human immunodeficiency virus: Utility of biomarkers for monitoring cervical carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1496.

Modulatory Effect of Human Immunodeficiency Virus on Circulating p53, miR-21, and miR-125b: Any Diagnostic Implication?

“…This is consistent with the findings of this study and could be due to sustained stimulation, dysfunction, and apoptosis of CD4+ T cells among HIV+ women [13]. It could also be attributable to a low level of circulating miR-let-7b since there was an inverse relationship between miR-21 and miR-let-7b [8]. Thus, miR-21 could be used as an early indicator of oncoviral activity and epithelial transformation among HIV+ women.…”

“…This would ultimately reduce late-stage presentation and cervical cancer-related death. In this study, we evaluated the levels of circulating miR-21, miR-146a, miR-155, miR-182, miR-200c, miR-let-7b, miR-125b, miR-143, miR-145, and p53 among HIV+ and HIV− women to identify early biomarkers of genetic instability [8,9]. For the first time, we demonstrated the singular modulatory effect of HIV on oncogenes and tumour suppressors among Human papillomavirus (HPV) and Epstein-Barr virus (EBV) seronegative women.…”

Modulatory effect of Human immunodeficiency virus on serum miR-21, miR-125b and p53 gene: Any prognostic implication?

“…13 It could also be due to a low level of circulating miR-let-7b considering the fact that there was an inverse relationship between miR-21 and miR-let-7b. 8 Thus, miR-21 could be used as an early indicator of oncoviral activity and epithelial transformation among HIV+ women.…”

“…This study evaluated the levels of normally downregulated oncomirs (miR-21, miR-146a, miR-155, miR-182, and miR-200c) and normally upregulated tumor suppressors (miR-let-7b, miR-125b, miR-143, miR-145, and p53 expression) associated with cervical cancer in the serum of women living with and without HIV in a bid to identify early indicators of genetic instability. 8,9…”