bims-lorfki 2020-08-23 papers

Issue of 2020‒08‒23
five papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

J Recept Signal Transduct Res. 2020 Aug 18. 1-11

CRNDE mediates the viability and epithelial-mesenchymal transition of renal cell carcinoma via miR-136-5p.

Yanhui Zhang, Xiaopeng Lan, Yizhen Wang, Chunlei Liu, Tao Cui.

Long non-coding RNAs (lncRNAs) regulate epithelial-mesenchymal transition (EMT) and the mutual adhesion and development of renal cell carcinoma (RCC). The underlying molecular mechanism of EMT and RCC cells in the treatment of RCC was less reported. In this study, the related functional lncRNA and miRNA in RCC tissues were predicted by bioinformatics analysis and verified by quantitative real-time PCR (qRT-PCR). The RNA interference technology was applied to measure the effects of the predicted lncRNAs and miRNAs on RCC cells. The expressions of EMT-related mRNAs and proteins were determined using qRT-PCR and Western-blot experiments. CRNDE was overexpressed and miR-136-5p was low-expressed in RCC. Upregulation of CRNDE could promote the viability, migration, invasion of RCC, while downregulation of CRNDE produced the opposite effects. Both the upregulation and downregulation of CRNDE alternated the protein expressions related to EMT, while miR-136-5p resulted in the opposite effects on CRNDE. Moreover, the promotive effect of overexpressed CRNDE on RCC cells could be blocked by miR-136-5p mimic. CRNDE can mediate miR-136-5p, promote the development of EMT and RCC cells, showing the potential to serve as a novel biomarker and therapeutic target in RCC treatment.

Keywords: RCC cell; epithelial–mesenchymal transition EMT; miR-136-5p; molecular mechanism

DOI: https://doi.org/10.1080/10799893.2020.1805629

Trends Biochem Sci. 2020 Aug 13. pii: S0968-0004(20)30174-2. [Epub ahead of print]

Mechanisms of Long Noncoding RNA Nuclear Retention.

Chun-Jie Guo, Guang Xu, Ling-Ling Chen.

Long noncoding RNAs (lncRNAs) are crucial regulators in diverse cellular contexts and biological processes. The subcellular localization of lncRNAs determines their modes of action. Compared to mRNAs, however, many mRNA-like lncRNAs are preferentially localized to the nucleus where they regulate chromatin organization, transcription, and different nuclear condensates. Recent studies have revealed the complex mechanisms that govern lncRNA nuclear retention. We review current understanding of how the transcription and processing of lncRNAs, motifs within lncRNAs, and trans-factors coordinately contribute to their nuclear retention in mammalian cells.

Keywords: RNA processing; cis-motifs; conservation; export; lncRNA; nuclear localization; trans-factors

DOI: https://doi.org/10.1016/j.tibs.2020.07.001

Kidney Blood Press Res. 2020 Aug 14. 1-16

Analysis of Differentially Expressed Long Noncoding RNA in Renal Ischemia-Reperfusion Injury.

Fen Liu, Yang Yang, Tong Liu, Jun Deng, Heng Zhang, Dan Luo, Yuan-Lei Lou.

BACKGROUND: Renal ischemia-reperfusion (IR) injury is one of the major causes of acute renal failure which seriously endangers the health and life of patients. Currently, there is still lack of comprehensive knowledge of the molecular mechanism of renal IR injury, and the regulatory role of long noncoding RNA (lncRNA) in renal IR damage remains poorly understood.AIM: The aim of this study was to analyze the expression spectrum of lncRNA in renal IR damage in mice and to explore specific lncRNA that may be involved in regulating the development of human renal IR injury.
METHODS: RNA-Seq was used to investigate the lncRNA profile of renal IR injury in a mouse model, and conservation analysis was performed on mouse lncRNAs with differential expression (fragments per kilobase of transcript per million mapped reads ≥2) by BLASTN. The potential functions and associated pathways of the differentially expressed lncRNA were explored by bioinformatics analysis. The cell hypoxia model was used to detect the expression of the candidate lncRNA.
RESULTS: Of the 45,923 lncRNA transcripts detected in the samples, and 5,868 lncRNAs were found to be significantly differentially expressed (p < 0.05 and fold change ≥ 2) in 24-h IR kidney tissue compared to the expression in the control group. It was found that 56 differently expressed mouse lncRNA transcripts have human homology by analyzing the conserved sequences. We also found that lncRNA-NONHSAT183385.1 expression significantly increased in HK2 cells after 24 h of hypoxia and increased further 6 h after reoxygenation, and after 24 h of reoxygenation it was dramatically downregulated, indicating that NONHSAT183385.1 may be involved in the pathophysiological process of renal tubular epithelial cells in response to ischemia in human renal IR.
CONCLUSION: Our study revealed differentially expressed lncRNAs in renal IR damage in mice and identified a set of conserved lncRNAs, which would help to explore lncRNAs that may play important regulatory roles in human renal IR injury.

Keywords: Long noncoding RNA; RNA sequencing; Renal ischemia-reperfusion injury

DOI: https://doi.org/10.1159/000508217

Cell Death Dis. 2020 Aug 19. 11(8): 660

LncRNA CDKN2B-AS1/miR-141/cyclin D network regulates tumor progression and metastasis of renal cell carcinoma.

Pritha Dasgupta, Priyanka Kulkarni, Shahana Majid, Yutaka Hashimoto, Marisa Shiina, Varahram Shahryari, Nadeem S Bhat, Laura Tabatabai, Soichiro Yamamura, Sharanjot Saini, Yuichiro Tanaka, Rajvir Dahiya.

The molecular heterogeneity of renal cell carcinoma (RCC) complicates the therapeutic interventions for advanced metastatic disease and thus its management remains a significant challenge. This study investigates the role of the lncRNA CDKN2B-AS1 and miR-141-3p interactions in the progression and metastasis of kidney cancer. Human renal cancer cell lines (ACHN and Caki1), normal RPTEC cells, tissue cohorts, and a series of in vitro assays and in vivo mouse model were used for this study. An overexpression of CDKN2B-AS1 was observed in RCC compared to normal samples in TCGA and our in-house SFVAMC tissue cohorts. Reciprocally, we observed reduced expression of miR-141 in RCC compared to normal in the same cohorts. CDKN2B-AS1 shares regulatory miR-141 binding sites with CCND1 and CCND2 genes. Direct interactions of CDKN2B-AS1/miR-141/Cyclin D1-D2 were confirmed by RNA immunoprecipitation and luciferase reporter assays indicating that CDKN2B-AS1/miR-141/Cyclin D1-D2 acts as a ceRNA network in RCC. Functionally, attenuation of CDKN2B-AS1 and/or overexpression of miR-141 inhibited proliferation, clonogenicity, migration/invasion, induced apoptosis in vitro and suppressed tumor growth in xenograft mouse model. Further, overexpression of CDKN2B-AS1 is positively correlated with poor overall survival of RCC patients. Expression of miR-141 also robustly discriminated malignant from non-malignant tissues and its inhibition in normal RPTEC cells induced pro-cancerous characteristics. CDKN2B-AS1 attenuation or miR-141 overexpression decreased CCND1/CCND2 expression, resulting in reduced RAC1/pPXN that are involved in migration, invasion and epithelial-mesenchymal transition. This study, for the first time, deciphered the role of CDKN2B-AS1/miR-141/Cyclin D axis in RCC and highlights this network as a promising therapeutic target for the regulation of EMT driven metastasis in RCC.

DOI: https://doi.org/10.1038/s41419-020-02877-0

NAR Cancer. 2020 Sep;2(3): zcaa015

Pan-cancer proteogenomic analysis reveals long and circular noncoding RNAs encoding peptides.

Ghofran Othoum, Emily Coonrod, Sidi Zhao, Ha X Dang, Christopher A Maher.

Recent studies show that annotated long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) encode for stable, functional peptides that contribute to human development and disease. To systematically discover lncRNAs and circRNAs encoding peptides, we performed a comprehensive integrative analysis of mass spectrometry-based proteomic and transcriptomic sequencing data from >900 patients across nine cancer types. This enabled us to identify 19,871 novel peptides derived from 8,903 lncRNAs. Further, we exploited open reading frames overlapping the backspliced region of circRNAs to identify 3,238 peptides that are uniquely derived from 2,834 circRNAs and not their corresponding linear RNAs. Collectively, our pan-cancer proteogenomic analysis will serve as a resource for evaluating the coding potential of lncRNAs and circRNAs that could aid future mechanistic studies exploring their function in cancer.

DOI: https://doi.org/10.1093/narcan/zcaa015