MCPIP1 RNase Is Aberrantly Distributed in Psoriatic Epidermis and Rapidly Induced by IL-17A
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Authors: Ruiz-Romeu, Ester; Ferran, Marta; Gimenez-Arnau, Ana; Bugara, Beata; Lipert, Barbara; Jura, Jolanta; Florencia, Edwin F.; Prens, Errol P.; Celada, Antonio; Pujol, Ramon M.; Santamaria-Babi, Luis F.
Abstract
ZC3H12A, which encodes the RNase monocyte chemotactic protein-induced protein 1 (MCPIP1), is upregulated in psoriatic skin and reduced to normal levels after clinical treatments with anti-IL-17A/IL-17R neutralizing antibodies. In IL-17A-stimulated keratinocytes, MCPIP1 is rapidly increased at the transcript and protein levels. Also, IL-17A was found to be the main inducer of ZC3H12A expression in keratinocytes treated with supernatants derived from a Streptococcus pyogenes-activated psoriatic ex vivo model based on the co-culture of psoriatic cutaneous lymphocyte-associated antigen (CLA(+)) T cells and lesional epidermal cells. Moreover, MCPIP1 was aberrantly distributed in the suprabasal layers of psoriatic epidermis. In psoriatic samples, IL-17A-stimulated epidermal cell suspensions showed an increased MCPIP1 expression, especially in the mid-differentiated cellular compartment. The knockdown of ZC3H12A showed that this RNase participates in the regulation of the mRNAs present in suprabasal differentiated keratinocytes. Furthermore, JAK/STAT3 inhibition prevented the IL-17A-dependent induction of MCPIP1. In the mouse model of imiquimod-induced psoriasis, Zc3h12a expression was abrogated in Il17ra(-/-) mice. These results support the notion that IL17A-mediated induction of MCPIP1 is involved in the regulation of local altered gene expression in suprabasal epidermal layers in psoriasis.
Association of lnc-IL17RA-11 with increased radiation sensitivity and improved prognosis of HPV-positive HNSCC
JOURNAL OF CELLULAR BIOCHEMISTRY
Authors: Song, Lianhao; Xie, Huanhuan; Tong, Fangjia; Yan, Bingqing; Zhang, Siwei; Fu, Enhui; Jing, Qingxu; Wei, Lanlan
Abstract
Human papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCC) has a far better prognosis than HPV negative HNSCC. Recent studies suggest that long noncoding RNA (lncRNA) moieties may play a role in HPV associated differential HNSCC prognoses. In this study, we examined differential expression of lncRNAs in HPV+ vs HPV- HNSCC using The Cancer Genome Atlas database. LncRNAs were categorized based on expression level and survival analysis. A group of eight lncRNAs was identified in which altered expression was associated with both HPV infection and better prognosis. Subsequently, genes coexpressed with these lncRNAs in HNSCC cells were sorted into corresponding co-expression modules. The lnc-IL17RA-11 coexpression module exhibited the greatest correlation with HPV infection and radiotherapy efficacy. We identified the lnc-IL17RA-11 transcription factor ER-alpha as the most likely HPV infection associated factor promoting increased lnc-IL17RA-11 levels. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment among lnc-IL17RA-11 co-expressed genes for functions related to DNA replication and cell proliferation. These observations are consistent with a model in which HPV infection upregulates transcription factor ER-alpha, which increases levels of lnc-IL17RA-11 and coexpressed genes that promote HNSCC cell sensitivity to radiotherapy, thereby improving disease prognosis.