bims-lorfki 2020-11-22 papers

Issue of 2020‒11‒22
five papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

Eur Rev Med Pharmacol Sci. 2020 Nov;pii: 23589. [Epub ahead of print]24(21): 11041-11051

Downregulation of long non-coding RNA DUXAP10 inhibits proliferation, migration, and invasion of renal cell carcinoma.

J Chen, X-F Wang, Y-C Qin, Y-B Gong, L Wang, N-C Li.

OBJECTIVE: Renal cell carcinoma (RCC) is the most common kidney malignancy that frequently leads to metastasis. Increasing evidence has shown that long non-coding RNAs (lncRNAs) play crucial roles affecting the progression of RCC. The role of lncRNA DUXAP10 in the evolution of RCC has not been defined yet. This project was designed to clarify the effects of DUXAP10 on the proliferation and tumorigenesis of RCC.PATIENTS AND METHODS: We examined the expression of DUXAP10 in the Cancer Genome Atlas (TCGA) and ONCOMINE oncology databases. Then, we performed quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to evaluate DUXAP10 expression in human RCC tissues and cell lines. The correlation between the expression of DUXAP10 and clinical characteristics of RCC patients was analyzed by univariate and Kaplan-Meier analyses. To unveil the biological function of DUXAP10 in cell cycle progression, cell growth, and invasion of RCC, we conducted knockdown experiments in vitro. qRT- PCR and western blotting assays were performed to further investigate the function of DUXAP10 in cancer biology.
RESULTS: The data from TCGA showed that the expression of DUXAP10 was upregulated in tissues of RCC compared with normal tissues. Moreover, ONCOMINE database analysis indicated that high DUXAP10 levels were correlated with high clinical stages, inferior TNM classification, and poor overall survival. Furthermore, the results indicated that knockdown of DUXAP10 remarkably inhibited the RCC cell growth, mobility, and invasion, in association with the upregulation of E-cadherin and downregulation of cyclin D, cyclin E, CDK4, N-cadherin, and vimentin.
CONCLUSIONS: Our findings highlight the oncogenic role of DUXAP10 in RCC and that DUXAP10 may serve as a novel predictive biomarker and therapeutic target for RCC.

DOI: https://doi.org/10.26355/eurrev_202011_23589

Front Oncol. 2020 ;10 602104

Cis- and Trans-Acting Expression Quantitative Trait Loci of Long Non-Coding RNA in 2,549 Cancers With Potential Clinical and Therapeutic Implications.

Wenzhi Li, Chaoqun Xu, Jintao Guo, Ke Liu, Yudi Hu, Dan Wu, Hongkun Fang, Yun Zou, Ziwei Wei, Zhong Wang, Ying Zhou, Qiyuan Li.

Many cancer risk loci act as expression quantitative trait loci (eQTLs) of transcripts including non-coding RNA. Long non-coding RNAs (lncRNAs) are implicated in various human cancers. However, the pathological and clinical impacts of the genetic determinants of lncRNAs in cancers remain largely unknown. In this study, we performed eQTL mapping of lncRNA expression (elncRNA) in 11 TCGA cancer types and characterized the biological processes of elncRNAs in the setting of genomic location, cancer treatment responses, and immune microenvironment. As a result, 10.86% of the cis-eQTLs and 1.67% of the trans-eQTLs of lncRNA were related to known genome-wide association studies (GWAS) cancer risk loci. The elncRNAs are significantly enriched for those which are previously annotated as predictive of drug sensitivities in cancer cell lines. We further revealed the downstream transcriptomic effectors of eQTL-elncRNA pairs. Our data specifically suggested that the genes affected by eQTL-elncRNA associations are enriched in the immune system processes and eQTL-elncRNA associations influence the constitution of tumor infiltrating lymphocytes. In ovarian cancer, the "rs34631313-AC092580.4" pair was associated with increased fraction of CD8+ T cells and M1 Macrophage; whereas in KIRC, the "rs9546285-LINC00426" pair was associated with increased fraction of CD8+ T cells and a decreased fraction of M2 macrophages. Our findings provide a systematic view of the transcriptomic impacts of the eQTL landscape of lncRNA in human cancers and suggest its strong potential relevance to cancer immunity and treatment.

Keywords: cancer; expression quantitative trait loci; instrumental variable analysis; long non-coding RNA; tumor immune microenvironment; tumor infiltrating lymphocytes

DOI: https://doi.org/10.3389/fonc.2020.602104

Eur Rev Med Pharmacol Sci. 2020 Nov;pii: 23558. [Epub ahead of print]24(21): 10920

LncRNA DLEU1 accelerates the malignant progression of clear cell renal cell carcinoma via regulating miRNA-194-5p.

G-Z He, S-Y Yu, Q-P Zhou, M-L Chen, Y-W Zhang, Y Zheng, Z-B Zhang, Z-Y Han, J Yu.

The article "LncRNA DLEU1 accelerates the malignant progression of clear cell renal cell carcinoma via regulating miRNA-194-5p, by G.-Z. He, S.-Y. Yu, Q.-P. Zhou, M.-L. Chen, Y.-W. Zhang, Y. Zheng, Z.-B. Zhang, Z.-Y. Han, J. Yu, published in Eur Rev Med Pharmacol Sci 2019; 23 (24): 10691-10698-DOI: 10.26355/eurrev_201912_19768-PMID 31858537" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19768.

DOI: https://doi.org/10.26355/eurrev_202011_23558

Front Genet. 2020 ;11 540094

Identification of RNA Transcript Makers Associated With Prognosis of Kidney Renal Clear Cell Carcinoma by a Competing Endogenous RNA Network Analysis.

Qiwei Yang, Weiwei Chu, Wei Yang, Yanqiong Cheng, Chuanmin Chu, Xiuwu Pan, Jianqing Ye, Jianwei Cao, Sishun Gan, Xingang Cui.

Objective: This study aims to identify several RNA transcripts associated with the prognosis of kidney renal clear cell carcinoma (KIRC).Methods: The differentially expressed mRNAs, lncRNAs, and miRNAs (DEmRNAs, DElncRNAs, and DEmiRNAs) between KIRC cases and controls were screened based on an RNA-seq dataset from The Cancer Genome Atlas (TCGA) database. Subsequently, miRcode, miRDB, and TargetScan database were used to predict interactions between lncRNAs, miRNAs and target mRNAs. Then, a ceRNA network was built using miRNAs-mRNAs and lncRNAs-miRNAs pairs. Functional analysis of mRNAs in ceRNA was performed. Finally, the survival analysis of RNA transcripts in ceRNA network and correlation analysis for key RNA regulators were carried out.
Results: There were 1527 DElncRNAs, 54 DEmiRNAs, and 2321 DEmRNAs. A ceRNA network was constructed among 81 lncRNAs, 9 miRNAs, and 197 mRNAs. Functional analysis showed that numerous mRNAs were significantly associated with regulation of cellular glucuronidation. In addition, 35 lncRNAs, 84 mRNAs and two miRNAs were significantly corelated to the survival of patients with KIRC (P < 0.05). Among them, miRNA-21 and miRNA-155 were negatively related to three lncRNAs (LINC00472, SLC25A5.AS1, and TCL6). Seven mRNA targets of miRNA-21 (FASLG, FGF1, TGFBI, ALX1, SLC30A10, ADCY2, and ABAT) and 12 mRNAs targets of miRNA-155 (STXBP5L, SCG2, SPI1, C12orf40, TYRP1, CTHRC1, TDO2, PTPRQ, TRPM8, ERMP1, CD36, and ST9SIA4) also acted as prognostic biomarkers for KIRC patients.
Conclusion: We screened numerous novel prognosis-related RNA markers for KIRC patients by a ceRNA network analysis, providing deeper understandings of prognostic values of RNA transcripts for KIRC.

Keywords: competing endogenous RNA network; kidney renal clear cell carcinoma; long non-coding RNAs; microRNAs; survival prognosis

DOI: https://doi.org/10.3389/fgene.2020.540094

Front Physiol. 2020 ;11 590027

Long Non-coding RNA LRNA9884 Promotes Acute Kidney Injury via Regulating NF-kB-Mediated Transcriptional Activation of MIF.

Yingying Zhang, Patrick Ming-Kuen Tang, Yangyang Niu, Cristina Alexandra García Córdoba, Xiao-Ru Huang, Chen Yu, Hui-Yao Lan.

Acute kidney injury (AKI) is one of the most common complications affecting hospitalized patients associated with an extremely high mortality rate. However, the underlying pathogenesis of AKI remains unclear that largely limits its effective management in clinic. Increasing evidence demonstrated the importance of long non-coding RNAs (lncRNAs) in the pathogenesis of AKI, because of their regulatory roles in transcription, translation, chromatin modification, and cellular organization. Here, we reported a new role of LRNA9884 in AKI. Using experimental cisplatin-induced AKI model, we found that LRNA9884 was markedly up-regulated in the nucleus of renal tubular epithelium in mice with AKI. We found that silencing of LRNA9884 effectively inhibited the production of inflammatory cytokines MCP-1, IL-6, and TNF-α in the mouse renal tubular epithelial cells (mTECs) under IL-1β stimulation in vitro. Mechanistically, LRNA9884 was involved into NF-κB-mediated inflammatory cytokines production especially on macrophage migration inhibitory factor (MIF). Collectedly, our study suggested LRNA9884 promoted MIF-triggered the production of inflammatory cytokines via NF-κB pathway after AKI injury. This study uncovered LRNA9884 has an adverse impact in AKI, and targeting LRNA9884 might represent a potential therapeutic target for AKI.

Keywords: AKI; NF-κB; inflammation; lncRNA; macrophage migration inhibitory factor

DOI: https://doi.org/10.3389/fphys.2020.590027