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Several studies showed that CDKN1A\/p21 is expressed at high levels ex vivo in cells from individuals who naturally control HIV-1 replication (HIC) and a recent study supports a coordinate regulation of ZC3H12A\/MCPIP1 and CDKN1A\/p21 transcripts in a model of renal carcinoma cells. Here, we explored the potential associations between mRNA expression of ZC3H12A\/MCPIP1 and CDKN1A\/p21 in HIC sustaining undetectable (elite controllers\u2013EC) or low (viremic controllers\u2013VC) viral loads.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found a selective upregulation of ZC3H12A\/MCPIP1 and CDKN1A\/p21 mRNA levels in PBMC from HIC compared with both ART\u2013suppressed and HIV\u2013negative control groups (P\u2264\u20090.02) and higher MCPIP1 and p21 proteins levels in HIC than in HIV-1 negative subjects. There was a moderate positive correlation (r\u2009\u2265\u20090.57; P\u2009\u2264\u20090.014) between expressions of both transcripts in HIC and in HIC combined with control groups. We found positive correlations between the mRNA level of CDKN1A\/p21 with activated CD4<jats:sup>+<\/jats:sup> T cells levels in HIC (r\u2009\u2265\u20090.53; P\u2009\u2264\u20090.017) and between the mRNA levels of both CDKN1A\/p21 (r\u2009=\u20090.74; P\u2009=\u20090.005) and ZC3H12A\/MCPIP1 (r\u2009=\u20090.58; P\u2009=\u20090.040) with plasmatic levels of sCD14 in EC. Reanalysis of published transcriptomic data confirmed the positive association between ZC3H12A\/MCPIP1 and CDKN1A\/p21 mRNA levels in CD4<jats:sup>+<\/jats:sup> T cells and monocytes from disparate cohorts of HIC and other HIV-positive control groups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These data show for the first time the simultaneous upregulation of ZC3H12A\/MCPIP1 and CDKN1A\/p21 transcripts in the setting of natural suppression of HIV-1 replication in vivo and the positive correlation of the expression of these cellular factors in disparate cohorts of HIV-positive individuals. The existence of a common regulatory pathway connecting ZC3H12A\/MCPIP1 and CDKN1A\/p21 could have a synergistic effect on HIV-1 replication control and pharmacological manipulation of these multifunctional host factors may open novel therapeutic perspectives to prevent HIV-1 replication and disease progression.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12977-020-00522-4","type":"journal-article","created":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T13:40:52Z","timestamp":1593697252000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Increased expression of CDKN1A\/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A\/MCPIP1"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6681-0987","authenticated-orcid":false,"given":"Suwellen S. 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