bims-lorfki 2021-01-17 papers

Issue of 2021‒01‒17
four papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

Front Oncol. 2020 ;10 573789

Long Non-Coding RNA LINC02747 Promotes the Proliferation of Clear Cell Renal Cell Carcinoma by Inhibiting miR-608 and Activating TFE3.

Xiang Ju, Yangyang Sun, Feng Zhang, Xiaohui Wei, Zhenguo Wang, Xiaozhou He.

With the rapid development of biotechnology, long noncoding RNAs (lncRNAs) have exhibited good application prospects in the treatment of cancer, and they may become new treatment targets for cancer. This study aimed to explore lncRNAs in clear cell renal cell carcinoma (ccRCC). Differentially expressed lncRNAs in 54 pairs of ccRCC tissues and para-carcinoma tissues were analyzed in The Cancer Genome Atlas (TCGA), and the most significant lncRNAs were selected and verified in ccRCC tissues. We found that lncRNA LINC02747 was highly expressed in ccRCC (P < 0.001) and was closely related to high TNM stage (P = 0.006) and histological grade (P = 0.004) and poor prognosis of patients (P < 0.001). In vivo and in vitro experiments confirmed that LINC02747 could promote the proliferation of ccRCC cells. We also found that LINC02747 regulated the proliferation of RCC cells by adsorbing miR-608. Subsequent mechanistic research showed that miR-608 is downregulated in ccRCC (P < 0.001), and overexpression of miR-608 inbibited the proliferation of RCC cells. Moreover, we found that TFE3 is a direct target gene of miR-608. MiR-608 regulated the proliferation of RCC cells by inhibiting TFE3. In conclusion, LINC02747 upregulates the expression of TFE3 by adsorbing miR-608, ultimately promoting the proliferation of ccRCC cells. The above findings indicate that LINC02747 acts as an oncogene in ccRCC and may be developed as a molecular marker for the diagnosis and prognosis of ccRCC. The LINC02747/miR-608/TFE3 pathway may become a new therapeutic target for ccRCC.

Keywords: LINC02747; TFE3 ; ccRCC; ceRNA; miR-608

DOI: https://doi.org/10.3389/fonc.2020.573789

Oxid Med Cell Longev. 2020 ;2020 6634247

Development and Validation of a Nine-Redox-Related Long Noncoding RNA Signature in Renal Clear Cell Carcinoma.

Xia Qi-Dong, Xun Yang, Jun-Lin Lu, Chen-Qian Liu, Jian-Xuan Sun, Cong Li, Shao-Gang Wang.

Background: Redox plays an essential role in the pathogeneses and progression of tumors, which could be regulated by long noncoding RNA (lncRNA). We aimed to develop and verify a novel redox-related lncRNA-based prognostic signature for clear cell renal cell carcinoma (ccRCC).Materials and Methods: A total of 530 ccRCC patients from The Cancer Genome Atlas (TCGA) were included in this study. All the samples were randomly split into training and test group at a 1 : 1 ratio. Then, we screened differentially expressed redox-related lncRNAs and constructed a novel prognostic signature from the training group using the least absolute shrinkage and selection operation (LASSO) and COX regression. Next, to verify the accuracy of the signature, we conducted risk and survival analysis, as well as the construction of ROC curve, nomogram, and calibration curves in the training group, test group, and all samples. Finally, the redox gene-redox-related lncRNA interaction network was constructed, and gene set enrichment analysis (GSEA) was performed to investigate the status of redox-related functions between high/low-risk groups.
Results: A nine-redox-related lncRNA signature consisted of AC025580.3, COLCA1, AC027601.2, DLEU2, AC004918.3, AP006621.2, AL031670.1, SPINT1-AS1, and LAMA5-AS1 was significantly associated with overall survival in ccRCC patients. The signature proved efficient, and thus, a nomogram was successfully assembled. In addition, the GSEA results demonstrated that two major redox-related functions were enhanced in the high-risk group ccRCC patients.
Conclusions: Our findings robustly demonstrate that the nine-redox-related lncRNA signature could serve as an efficient prognostic indicator for ccRCC.

DOI: https://doi.org/10.1155/2020/6634247

Clin Chim Acta. 2021 Jan 07. pii: S0009-8981(21)00001-2. [Epub ahead of print]

The Epitranscriptome of Long Noncoding RNAs in Metabolic Diseases.

Linjie Yin, Xiao Zhu, Petr Novák, Le Zhou, Ling Gao, Min Yang, GuoJun Zhao, Kai Yin.

Long noncoding RNAs (lncRNAs) have abundant content and extensive functions that regulate the expression of genes at multiple levels. Recently, transcriptome-wide analysis confirmed that RNA can undergo various chemical modifications in response to stimulation by the environment that further determine the action mechanisms of RNAs and expand the diversity of the transcriptome. Modifications that occur in lncRNAs can affect their expression and the regulation of downstream molecules by changing the secondary structure, splicing, degradation or molecular stability of lncRNAs. During the development of metabolic diseases, reversible RNA modifications show a complex transcriptional landscape. Although a wide quantity and variety of lncRNA modifications have been identified, the knowledge regarding their underlying actions in alcohol use disorders (AUDs), osteoporosis, obesity, and cardiovascular disease (CVD) is still in its infancy. Herein, we will focus on the epitranscriptomic modifications that occur on lncRNAs and the crosstalk between them that affect metabolic diseases.

Keywords: 5-methylcytidine (m5C); Epitranscriptomics; Long Noncoding RNA (lncRNA); Metabolic Disease; N6-methyladenosine (m6A); Pseudouridine (ψ)

DOI: https://doi.org/10.1016/j.cca.2021.01.001

BMC Nephrol. 2021 Jan 12. 22(1): 27

PTGER3 and MMP-2 play potential roles in diabetic nephropathy via competing endogenous RNA mechanisms.

Yue Yu, Yuan-Yuan Jia, Meng Wang, Lin Mu, Hong-Jun Li.

BACKGROUND: Diabetic nephropathy (DN) is a primary complication of diabetes mellitus (DM). The pathology of DN is still vague, and diagnostic accuracy is not enough. This study was performed to identify miRNAs and genes that have possibilities of being used as therapeutic targets for DN in type 2 DM.METHODS: Human miRNA data GSE51674 and gene data GSE111154 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) in the kidney between control and DN patients were screened out. The competing endogenous RNA (ceRNA) network was constructed, and key lncRNA-miRNA-mRNA pairs were selected accordingly. Potential drugs targeting DEGs were screened out and validated using PCR analysis.
RESULTS: Totally, 83 DEmiRNAs and 293 DEGs were identified in GSE51674 and GSE111154, respectively. Thirteen of the top 20 DEmiRNAs (10 up and 10 down) targeted to 47 DEGs. In the ceRNA network, RP11-363E7.4/TTN-AS1/HOTAIRM1-hsa-miR-106b-5p-PTGER3 and LINC00960-hsa-miR-1237-3p-MMP-2 interaction pairs were identified as the key ceRNA network. Interestingly, PTGER3 and hsa-miR-1237-3p were downregulated, and MMP-2 and hsa-miR-106b-5p were upregulated in the kidney of patients with DN compared with normal controls, respectively. PTGER3 and MMP-2 were targeted by drugs including iloprost, treprostinil, or captopril, and the deregulation of the two genes was confirmed in the plasma samples from patients with DN as compared with controls.
CONCLUSIONS: We speculated that the RP11-363E7.4/TTN-AS1/HOTAIRM1-hsa-miR-106b-5p-PTGER3 and LINC00960-hsa-miR-1237-3p-MMP-2 networks were associated with diabetic renal injury.

Keywords: Diabetic nephropathy; Microarray; Molecular biology; Type 2 diabetes mellitus; microRNAs

DOI: https://doi.org/10.1186/s12882-020-02194-w