Elevated m 6 A RNA modifications associate with immune dysregulation and cancer in people with HIV-1

Tarun Mishra; Shraddha Tripathi; Jack T Stapleton; Li Wu

doi:10.1186/s12885-026-15874-x

Back

Elevated m 6 A RNA modifications associate with immune dysregulation and cancer in people with HIV-1

Journal article

Open access

Peer reviewed

Elevated m 6 A RNA modifications associate with immune dysregulation and cancer in people with HIV-1

Tarun Mishra, Shraddha Tripathi, Jack T Stapleton and Li Wu

BMC cancer

03/21/2026

DOI: 10.1186/s12885-026-15874-x

PMID: 41862833

Files and links (1)

url

https://doi.org/10.1186/s12885-026-15874-xView

Published (Version of record) Open Access

Abstract

Background N6-methyladenosine (m6A) modifications of human immunodeficiency virus type 1 (HIV-1) and cellular RNA contribute to regulation of viral and host gene expression. RNA m6A dysregulation has been implicated in multiple cancers. However, the role of m6A modifications in HIV-1-associated cancers remains unclear. Here, we aim to address this important question using clinical samples. Methods Using enzyme-linked immunosorbent assay (ELISA), RNA m6A levels were quantified in peripheral blood mononuclear cells (PBMCs) from 43 de-identified people living with HIV-1 (PLWH), comparing those with cancer (n = 15) to those without cancer (n = 28). Correlation analyses were performed to evaluate the associations between m6A levels and HIV-1 RNA copies, CD4+ T-cell counts, and age of PLWH. The mRNA and protein expression of m6A regulatory genes was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. Furthermore, quantitative transcriptomic profiling of 84 type I interferon (IFN-I)-responsive genes was performed using an RT-qPCR array. Results We observed that HIV-1 viral load in the cancer group was higher than the non-cancer group. m6A levels of PBMCs were 2.8-fold higher in the cancer group and correlated with the expression of some m6A regulatory genes and proteins. Higher m6A levels were positively associated with HIV-1 RNA copies and negatively associated with CD4+ T-cell counts and age. Transcriptomic analysis of 84 IFN-I-responsive genes revealed upregulation of many pro-inflammatory and interferon-stimulated genes, along with downregulation of some genes in PLWH with cancer. Conclusions Our findings suggest that HIV-1 infection and cancer-mediated m6A reprogramming may contribute to multifaceted chronic immune activation and malignancy in PLWH. Our results also highlight a post-transcriptional mechanism linking HIV-1 persistence to cancer risk.

HIV-1 infection

N 6-methyladenosine (m6A)

Antiretroviral therapy (ART)

Type-I interferon (IFN-I)

IFN-responsive genes

Peripheral blood mononuclear cells (PBMCs)

People living with HIV-1 (PLWH)

Cancer

Details

Title: Subtitle: Elevated m 6 A RNA modifications associate with immune dysregulation and cancer in people with HIV-1
Creators: Tarun Mishra - University of Iowa
Shraddha Tripathi - University of Iowa
Jack T Stapleton - University of Iowa
Li Wu - University of Iowa
Resource Type: Journal article
Publication Details: BMC cancer
DOI: 10.1186/s12885-026-15874-x
PMID: 41862833
eISSN: 1471-2407
Publisher: Springer Nature
Grant note: R33 AI169659 / NIAID NIH HHS R61 AI169659 / NIAID NIH HHS P30CA086862 (supplement 24S1 and 25S1) and R61/R33AI169659 / U.S. National Institutes of Health BX000207 / Veterans Administration Health Service P30 CA086862 / NCI NIH HHS
Language: English
Electronic publication date: 03/21/2026
Academic Unit: Microbiology and Immunology; Infectious Diseases; Internal Medicine
Record Identifier: 9985144718702771

Metrics

1 Record Views