bims-lorfki 2022-01-23 papers

J Healthc Eng. 2022 ;2022 7768963

Long Noncoding RNA ZFAS1 Protects HK-2 Cells against Sepsis-Induced Injury through Targeting the miR3723p/PPARα Axis.

In septic acute kidney injury, one of the main purposes of long noncoding RNA (lncRNA) ZFAS1 is still unclear. This study is intended to analyze the effects of lncRNA ZFAS1 on the septic AKI in the HK-2 cell line. Materials and Methods. In order to construct an in vitro model of septic AKI, HK-2 cells have been treated with lipopolysaccharides. CCK-8 assay has been utilized to check the viability of HK-2 cells. The contents of inflammatory cytokines (that includes IL-1β, TNF-α, and IL-6) have been marked with enzyme-linked immune sorbent assay (ELISA). Cell apoptosis was assessed by TUNEL staining. To detect the expression of lncRNA ZFAS1 and microRNA-372-3p, quantitative reverse-transcription PCR has been used. And to confirm the connection among genes, luciferase reporter assay has been applied. Results. Overexpression of ZFAS1 alleviated LPS-induced HK-2 cell injury. ZFAS1 positively regulated expression of α receptor activated by peroxisome proliferation (PPARα) through competitive linkage with miR-372-3p. In addition, over expression of miR-372-3p counteracted the protective effect of upward regulation of ZFAS1 on LPS-induced HK-2 cell damage, which could be reversed by over expression of PPARα. Conclusion. It is concluded that, in LPS-induced HK-2 cell injury, ZFAS1 has a protective role via modulating the miR-372-3p/PPARα axis, suggesting the potential of ZFAS1 as a protective target for septic AKI.

DOI: https://doi.org/10.1155/2022/7768963

Am J Pathol. 2022 Jan 18. pii: S0002-9440(22)00009-8. [Epub ahead of print]

An integrative analysis framework for identifying the prognostic markers from multidimensional RNA data of clear cell renal cell carcinoma.

Peng-Ying Wang, Shihui Yang, Yun-Juan Bao.

The altered regulatory status of lncRNA, miRNA, and mRNA and their interactions have been reported to play critical roles in tumor proliferation, metastasis, and progression, which will ultimately produce influences on prognosis in cancer. However, there is still limited study of comprehensive identification of prognostic biomarkers from combined datasets of the three RNA types in the highly metastatic clear cell renal cell carcinoma (ccRCC). In this study, we employed an integrative analysis framework of functional genomics approaches and machine learning methods to the lncRNA, miRNA, and mRNA data and identified 16 RNAs (3 lncRNAs, 6 miRNAs, and 7 mRNAs) of prognostic value with 9 of them novel. We then established a 16-RNA-based score for prognosis prediction of ccRCC with significance (p-value < 0.0001). The AUC for the score model is 0.868-0.870 in the training cohort and 0.714-0.778 in the validation cohort. Construction of the lncRNA-miRNA-mRNA interaction network showed that the downstream mRNAs and upstream lncRNAs in the network initiated from the miRNA or lncRNA markers exhibit significant enrichment in functional classifications associated with cancer metastasis, proliferation, progression, or prognosis. The functional analysis provided clear support for the role of the RNA biomarkers in predicting cancer prognosis. Our study provides promising biomarkers for predicting prognosis of ccRCC using multidimensional RNA data and the findings will facilitate potential clinical applications of the biomarkers.

DOI: https://doi.org/10.1016/j.ajpath.2021.12.009

Kidney Blood Press Res. 2022 Jan 17. 1-8

LncRNA Dlx6os1 Accelerates Diabetic Nephropathy Progression by Epigenetically Repressing SOX6 via Recruiting EZH2.

Yan-Xia Chen, Shu-Ying Zhu, Chong Huang, Cheng-Yun Xu, Xiang-Dong Fang, Wei-Ping Tu.

INTRODUCTION: Diabetic nephropathy (DN) is the leading cause of kidney failure worldwide. To explore the pathogenesis and effective biological target of DN is beneficial to seeking novel treatment strategies.
OBJECTIVE: This study aimed to investigate the role of the lncRNA Dlx6os1/SOX6/EZH2 axis in DN progression.
METHODS: PAS staining was performed to evaluate extracellular matrix accumulation; ELISA was carried out to assess the levels of urine microalbumin and blood glucose concentration; RT-qPCR was carried out to detect the levels of lncRNA Dlx6os1, TNF-α, IL-1β, IL-6, SOX6, and EZH2. Western blot was performed to assess the levels of Col-IV, FN, TGF-β1, and SOX6 proteins. RIP assay was carried out to verify the interaction between lncRNA Dlx6os1 and EZH2. ChIP-qPCR was conducted to verify the interaction between EZH2 and SOX6 promoter.
RESULTS: Our results illustrated that lncRNA Dlx6os1 was highly expressed in DN mice and HG-induced SV40 MES13 cells. LncRNA Dlx6os1 knockdown inhibited HG-induced SV40 MES13 cell proliferation, fibrosis, and inflammatory cytokine release. LncRNA Dlx6os1 inhibited SOX6 expression by recruiting EZH2 in HG-SV40 MES13 cells, and SOX6 mediated the effects of lncRNA Dlx6os1 on proliferation, fibrosis, and inflammatory factor release of HG-induced SV40 MES13 cells.
CONCLUSION: LncRNA Dlx6os1 accelerates the progression of DN by epigenetically repressing SOX6 via recruiting EZH2.

Keywords: Diabetic nephropathy; Enhancer of zeste homolog 2; LncRNA Dlx6os1; SOX6

DOI: https://doi.org/10.1159/000520490