bims-lorfki 2021-12-26 papers

Issue of 2021‒12‒26
two papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

Int J Gen Med. 2021 ;14 9773-9787

The Role of Critical N6-Methyladenosine-Related Long Non-Coding RNAs and Their Correlations with Immune Checkpoints in Renal Clear Cell Carcinoma.

Wen Deng, Gongxian Wang, Huanhuan Deng, Yan Yan, Ke Zhu, Ru Chen, Xiaoqiang Liu, Luyao Chen, Tao Zeng, Bin Fu.

Purpose: This study aimed to evaluate the functions of critical N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) and their correlations with immunotherapeutic targets in clear cell renal cell carcinoma (ccRCC).Methods: m6A-related lncRNAs were analyzed using the dataset from The Cancer Genome Atlas database via Pearson correlation analysis. Then, their prognostic functions in patients with ccRCC were determined via univariate Cox analysis. A prognostic m6A-related lncRNA signature (MRLS) in ccRCC was established using the least absolute shrinkage and selection operator (LASSO) Cox regression model. In addition, the correlations between these prognostic m6A-related lncRNAs with immune checkpoints were further evaluated in clinical samples.
Results: MRLS was established by the LASSO Cox regression model on the basis of seven prognostic m6A-related lncRNAs. The risk score for each patient was calculated using the MRLS model, and the patients were further stratified into high- and low-risk subgroups. The MRLS model was validated with a robust prognostic ability by the stratification analysis. On the basis of age, grade, stage, and risk score, a nomogram was developed with a strong reliability in forecasting the overall survival percentages of the patients with ccRCC. Moreover, seven prognostic m6A-related lncRNAs enrolled in the MRLS model were found to be correlated with various immunotherapeutic targets, namely, PD-1, PD-L1, CTLA4, and LAG3, and the expression levels of which in the high-risk subgroup were significantly higher than those in the low-risk subgroup. The significant correlations between LINC00342 and the aforementioned immunotherapeutic targets were also confirmed in clinical samples.
Conclusion: In this study, seven m6A-related lncRNAs were identified as potential biomarkers for forecasting the prognosis of patients with ccRCC and evaluating the efficacy of immunotherapy for these patients. Furthermore, a prognostic and predictive MRLS model with a high reliability was constructed to predict the overall survival probability of patients with ccRCC.

Keywords: N6-methyladenosine modification; immunotherapy; long non-coding RNA; prognosis; renal cell carcinoma

DOI: https://doi.org/10.2147/IJGM.S344771

Front Genet. 2021 ;12 774155

Construction and Analysis of Immune Infiltration-Related ceRNA Network for Kidney Stones.

Yuqi Xia, Xiangjun Zhou, Zehua Ye, Weimin Yu, Jinzhuo Ning, Yuan Ruan, Run Yuan, Fangyou Lin, Peng Ye, Di Zheng, Ting Rao, Fan Cheng.

Purpose: Kidney stones is a common medical issue that mediates kidney injury and even kidney function loss. However, the exact pathogenesis still remains unclear. This study aimed to explore the potential competing endogenous RNA (ceRNA)-related pathogenesis of kidney stones and identify the corresponding immune infiltration signature. Methods: One mRNA and one long non-coding RNA (lncRNA) microarray dataset was obtained from the GEO database. Subsequently, we compared differentially expressed mRNAs (DE-mRNAs) and lncRNAs between Randall's plaques in patients with calcium oxalate (CaOx) stones and controls with normal papillary tissues. lncRNA-targeted miRNAs and miRNA-mRNA pairs were predicted using the online databases. lncRNA-related DE-mRNAs were identified using the Venn method, and GO and KEGG enrichment analyses were subsequently performed. The immune-related lncRNA-miRNA-mRNA ceRNA network was developed. The CIBERSORT algorithm was used to estimate the rate of immune cell infiltration in Randall's plaques. The ceRNA network and immune infiltration were validated in the glyoxylate-induced hyperoxaluric mouse model and oxalate-treated HK-2 cells. Results: We identified 2,340 DE-mRNAs and 929 DE-lncRNAs between Randall's plaques in patients with CaOx stones and controls with normal papillary tissues. lncRNA-related DE-mRNAs were significantly enriched in extracellular matrix organization and collagen-containing extracellular matrix, which were associated with kidney interstitial fibrosis. The immune-related ceRNA network included 10 lncRNAs, 23 miRNAs, and 20 mRNAs. Moreover, we found that M2 macrophages and resting mast cells were differentially expressed between Randall's plaques and normal tissues. Throughout kidney stone development, kidney tubular injury, crystal deposition, collagen fiber deposition, TGF-β expression, infiltration of M1 macrophages, and activation of mast cells were more frequent in glyoxylate-induced hyperoxaluric mice compared with control mice. Nevertheless, M2 macrophage infiltration increased in early stages (day 6) and decreased as kidney stones progressed (day 12). Furthermore, treatment with 0.25 and 0.5 mM of oxalate for 48 h significantly upregulated NEAT1, PVT1, CCL7, and ROBO2 expression levels and downregulated hsa-miR-23b-3p, hsa-miR-429, and hsa-miR-139-5p expression levels in the HK-2 cell line in a dose-dependent manner. Conclusion: We found that significant expressions of ceRNAs (NEAT1, PVT1, hsa-miR-23b-3p, hsa-miR-429, hsa-miR-139-5p, CCL7, and ROBO2) and infiltrating immune cells (macrophages and mast cells) may be involved in kidney stone pathogenesis. These findings provide novel potential therapeutic targets for kidney stones.

Keywords: calcium oxalate; ceRNA; glyoxylate; immune cell infiltration; kidney stones

DOI: https://doi.org/10.3389/fgene.2021.774155