bims-lorfki 2020-11-01 papers

Issue of 2020‒11‒01
four papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

Klin Onkol. 2020 ;33(5): 340-349

Long non-coding RNAs and renal cell carcinoma.

Fedorko Michal, Febu, Bohošová Júlia, Poprach Alexandr, Pacík Dalibor.

BACKGROUND: To provide an overview of the importance of long non-coding RNAs (lncRNAs) in the pathogenesis of renal cell carcinoma and their utility as bio-markers for dia-gnosis, prognosis and prediction of treatment response.MATERIALS AND METHODS: A literature search in the Pubmed and Web of Science databases using the keywords variations of “long non-coding RNA” (“lncRNA”, “long noncoding RNA”, “long non-coding RNA”) and “renal cell carcinoma” (“renal cancer”, “renal cell carcinoma”, “kidney cancer”) was performed. The results related to the pathogenesis, dia-gnosis, prognosis and use as therapeutic targets were separated.
RESULTS: Long non-coding RNAs regulate gene expression at different levels. They act both as oncogenes and tumor suppressors. The mechanism of their action has not been fully elucidated, but they are actively involved in the regulation of hypoxia inducible factors pathway, epithelial-mesenchymal transition, cell proliferation, cell cycle regulation, apoptosis, local invasion and development of metastases. Aberrant expression in tumor tissue compared to healthy parenchyma and the correlation of expression levels with clinical-pathological features allow the potential use of many lncRNAs as bio-markers for early detection and prognosis of the disease, including the response to targeted therapy. In vitro assays indicate the potential use of lncRNAs as therapeutic targets.
CONCLUSION: Our knowledge of long non-coding RNAs in relation to renal cell carcinoma is increasing rapidly. At present, some of them can be considered as promising bio-markers. Further research is needed before they can be introduced into routine clinical practice.

Keywords: biomarker; diagnosis; long non-coding RNA; prognosis; renal cell carcinoma

DOI: https://doi.org/10.14735/amko2020340

Diabetes Metab Syndr Obes. 2020 ;13 3551-3560

LncRNA SNHG16 Aggravates High Glucose-Induced Podocytes Injury in Diabetic Nephropathy Through Targeting miR-106a and Thereby Up-Regulating KLF9.

Xin He, Xiuya Zeng.

Introduction: Diabetic nephropathy (DN) is one of the major complications of diabetes and podocyte injury plays an important role in the DN pathogenesis. MicroRNA (miR)-106a is predicated to be a target of long noncoding RNA (lncRNA) SNHG16 and has been identified as a therapeutic biomarker for diabetic kidney diseases. However, the role of SNHG16/miR-106a axis in DN has not been illustrated. This study aimed to investigate whether SNHG16 could regulate podocyte injury via miR-106a in DN and uncover the underlying mechanism.Methods: MPC5 podocytes were treated with control or high glucose (HG) medium, and then miR-106a level was measured. MPC5 cells that exposed to HG were overexpressed with miR-106a or not, following by overexpression with or without KLF9 or SNHG16. Then, cell viability, apoptosis, reactive oxygen species and the protein expression of synaptopodin and podocin were evaluated.
Results: MiR-106a was down-regulated in the serum of DN patients and HG-induced MPC5 podocytes. Overexpression of miR-106a suppressed HG-induced decrease in cell viability, Bcl-2, synaptopodin and podocin expression, increase in ROS, apoptotic cells, Bax and cleaved-caspase 3 expression. MiR-106a could bind to both KLF9 and lncRNA SNHG16, which were up-regulated in the serum of DN patients and HG-induced MPC5 podocytes. The level of miR-106a was decreased by SNHG16 overexpression and miR-106a overexpression reduced KLF9 expression. Furthermore, overexpression of KLF9 or SNHG16 blunted the protective effects of miR-106a on HG-induced MPC5 injury.
Discussion: LncRNA SNHG16 could promote HG-stimulated podocytes injury via targeting miR-106a to enhance KLF9 expression. The intervention of SNHG16/miR-106a/KLF9 may be a therapeutic treatment for DN.

Keywords: diabetic nephropathy; high glucose; long noncoding RNA; miR-106a; podocyte

DOI: https://doi.org/10.2147/DMSO.S271290

Onco Targets Ther. 2020 ;13 10185-10196

LINC02738 Participates in the Development of Kidney Cancer Through the miR-20b/Sox4 Axis.

Chao Han, Bin Xu, Lin Zhou, Long Li, Chao Lu, Guo-Peng Yu, Yu-Shan Liu.

Background: Long non-coding RNAs (lncRNAs) can affect tumorigenesis. Data from The Cancer Genome Atlas (TCAG) suggest that LINC02783 is highly expressed in renal cell carcinoma (RCC) and is expected to be a potential biological target. We conducted this study to verify this.Patients and Methods: We conducted this study to verify the opinion that "LINC02783 is highly expressed in renal cell carcinoma (RCC) and is expected to be a potential biological target". We employed quantitative real-time polymerase chain reaction (qRT-PCR) to test LINC02783 expression in RCC tissues, CKK-8 assay and transwell assay to assess the viability and invasion of RCC cells, Western blot to quantify Sox-4 expression, dual-luciferase reporter (DLR) assay and RNA immunoprecipitation (RIP) assay to analyze the interaction between LINC02783 and miR-20b, in vivo experiments to test tumor formation.
Results: We detected high LINC02783 expression in RCC patients. Patients with higher LINC02783 levels had a markedly poorer prognosis. In vitro and in vivo, the down-regulation of LINC02783 suppressed the viability and invasion of RCC cells. The DLR assay results revealed that LINC02783 enhanced Sox-4 expression by regulating miR-20b. LINC02783 can act as a sponge for miR-20b to inhibit Sox-4 expression.
Conclusion: LINC02783 is highly expressed in RCC patients and indicates a poor prognosis. LINC02783 can affect the occurrence and progression of RCC through the miR-20b/Sox-4 axis, making it a promising target for the treatment of RCC.

Keywords: LINC02783; Sox-4; The Cancer Genome Atlas; miR-20b; prognosis; renal cell carcinoma

DOI: https://doi.org/10.2147/OTT.S262046

Biomed Pharmacother. 2020 Oct 21. pii: S0753-3322(20)31001-5. [Epub ahead of print]132 110808

Long non-coding RNA BLACAT1, a novel promising biomarker and regulator of human cancers.

Min Zhu, Xiao Li, Shengtao Zhu, Peng Li, Li Min, Shutian Zhang.

Emerging evidence has shown that aberrantly expressed long noncoding RNAs (lncRNAs) play a vital role in various biological processes of tumorigenesis. Bladder cancer associated transcript 1 (BLACAT1) is a novel lncRNA located on chromosome 1q32.1, which regulated multiple downstream targets via serving as a "sponge" for their corresponding microRNAs or by directly interacting with various regulating proteins. In this review, we summarized the role of BLACAT1 in the development and progression of different cancers. We also highlighted that BLACAT1 could be utilized as a potential biomarker and therapeutic target for human cancers.

Keywords: BLACAT1; Biomarker; Cancer; Long non-coding RNA

DOI: https://doi.org/10.1016/j.biopha.2020.110808