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SERPINA3 is a key modulator of HNRNP-K transcriptional activity against oxidative stress in HCC

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Title
SERPINA3 is a key modulator of HNRNP-K transcriptional activity against oxidative stress in HCC
Author(s)
Eunkyong Ko; KimJong-Seo Kim; Jong Woo Bae; Jeesoo Kim; Sung-Gyoo Park; Guhung Jung
Publication Date
2019-06
Journal
REDOX BIOLOGY, v.24, no., pp.UNSP101217 -
Publisher
ELSEVIER SCIENCE BV
Abstract
© 2019 The Authors Most studies about serpin peptidase inhibitor, clade A member 3 (SERPINA3) has been limited to its inhibitory functions and mechanisms. Herein, we report a novel role of SERPINA3 in transcriptional regulation of HCC progression-related genes. Among 19 selected genes through HCC cell isolation system based on telomere length, microarray analyses, and cell-based studies, SERPINA3 was the strongest determinant of increases in telomere length, HCC cell proliferation, survival, migration, and invasion. We also found that SERPINA3 strongly interacted with heterogeneous nuclear ribonucleoprotein K (HNRNP-K) under H 2 O 2 exposure, and the oxidation-elicited SERPINA3-HNRNP-K complex enhanced the promoter activities and transcript levels of a telomere-relating gene (POT1) and HCC-promoting genes (UHRF1 and HIST2H2BE). Intriguingly, the inhibition of SERPINA3 oxidation rendered the transcriptional activity of the SERPINA3-HNRNP-K complex suppressed. Moreover, the co-immunoprecipitated HNRNP-K with SERPINA3 quantitatively correlated with not only the level of SERPINA3 oxidation but also the level of POT1, UHRF1, and HIST2H2BE transcripts and telomere length in HCC tissues. Therefore, the upregulated transcriptional activity of HNRNP-K mediated by SERPINA3 promotes HCC cell survival and proliferation and could be an indicator of poor prognosis for HCC patients
URI
https://pr.ibs.re.kr/handle/8788114/6072
ISSN
2213-2317
Appears in Collections:
Center for RNA Research(RNA 연구단) > Journal Papers (저널논문)
Files in This Item:
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