bims-lorfki 2021-02-07 papers

Issue of 2021‒02‒07
four papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

Genomics. 2021 Jan 28. pii: S0888-7543(21)00042-2. [Epub ahead of print]

A panel of eight autophagy-related long non-coding RNAs is a good predictive parameter for clear cell renal cell carcinoma.

Cheng-Peng Gui, Jia-Zheng Cao, Lei Tan, Yong Huang, Yi-Ming Tang, Peng-Ju Li, Yu-Hang Chen, Jun Lu, Hao-Hua Yao, Zhen-Hua Chen, Yi-Hui Pan, Yun-Lin Ye, Zi-Ke Qin, Wei Chen, Jin-Huan Wei, Jun-Hang Luo.

Clear-cell renal cell carcinoma (ccRCC) carries a variable prognosis. Prognostic biomarkers can stratify patients according to risk, and can provide crucial information for clinical decision-making. We screened for an autophagy-related long non-coding lncRNA (lncRNA) signature to improve postoperative risk stratification in The Cancer Genome Atlas (TCGA) database. We confirmed this model in ICGC and SYSU cohorts as a significant and independent prognostic signature. Western blotting, autophagic-flux assay and transmission electron microscopy were used to verify that regulation of expression of 8 lncRNAs related to autophagy affected changes in autophagic flow in vitro. Our data suggest that 8-lncRNA signature related to autophagy is a promising prognostic tool in predicting the survival of patients with ccRCC. Combination of this signature with clinical and pathologic parameters could aid accurate risk assessment to guide clinical management, and this 8-lncRNAs signature related to autophagy may serve as a therapeutic target.

Keywords: Autophagic flux; Autophagy; Long non-coding RNA; Prognostic signature; Renal clear cell carcinoma; TEM; Western blot

DOI: https://doi.org/10.1016/j.ygeno.2021.01.016

Bioengineered. 2021 Jan 31.

An epithelial-mesenchymal transition-Related Long Non-Coding RNA signature to predict overall survival and immune microenvironment in Kidney Renal Clear Cell Carcinoma.

Yong-Biao Cheng, Sen Li, You-Peng Zhang, Zhao-Hui Zhu, Ning Zhao.

Kidney renal clear cell carcinoma (ccRCC) is a malignant tumor originating from renal tubular epithelium, lncRNAs can regulate the occurrence and development of EMT by targeting EMT transcription factors. We constructed a new survival signature based on EMT-related differentially expressed lncRNAs obtained from The Cancer Genome Atlas (TCGA-KIRC). We first determined 1377 EMT-related lncRNAs, lncRNA AL035661.1 with the largest correlation coefficient and the target gene was PFN2 (cor=0.843; P=1.37E-146). Meanwhile, we found an AUC of 0.758 in our signature and we predicted the AUC values of the patients' 1, 2, 3-year survival rate as 0.768, 0.749, and 0.762 in TCGA cohort, respectively. Multivariate COX analysis was performed to determine if risk score was an independent prognostic predictor of OS. The results indicated that our risk score can be an independent predictor for OS (Univariate: HR=1.350, 95% CI=1.276-1.428, P<0.001; Multivariate: HR=1.295, 95% CI=1.201-1.396, P<0.001). We identified novel EMT-related lncRNAs markers for ccRCC prognosis. The underlying mechanism between EMT-related lncRNAs in ccRCC and tumor immunity is still unclear and requires further study.

Keywords: Kidney renal clear cell carcinoma; data mining; epithelial-mesenchymal transition; lncRNAs

DOI: https://doi.org/10.1080/21655979.2021.1880718

Clin Exp Nephrol. 2021 Feb 06.

Association of serum lncRNA H19 expression with inflammatory and oxidative stress markers and routine biochemical parameters in chronic kidney disease.

Hamza Malik Okuyan, Serdar Dogan, Menderes Yusuf Terzi, Mehmet A Begen, Faruk Hilmi Turgut.

BACKGROUND: Chronic kidney disease (CKD) is a disorder that affects millions worldwide, and current treatment options aiming at inhibiting the progression of kidney damage are limited. Long noncoding RNA (lncRNA) H19 is one of the first explored lncRNAs and its deregulation is associated with renal pathologies, such as renal cell injury and nephrotic syndrome. However, there is still no research investigating the connection between serum lncRNA H19 expressions and clinical outcomes in CKD patients. Therefore, we investigated the relation of serum lncRNA H19 expressions with routine biochemical parameters, inflammatory cytokines, oxidative stress and mineralization markers in advanced CKD patients.METHODS: lncRNA H19 serum levels from 56 CKD patients and 20 healthy controls were analyzed with reverse-transcription quantitative polymerase chain reaction method. Serum tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and osteocalcin (OC) levels were measured with enzyme linked-immunosorbent assay. Total antioxidant status (TAS) and total oxidative status (TOS) levels were evaluated by the routine measurement method.
RESULTS: We found that lncRNA H19 expressions were upregulated in patients with CKD compared to the controls. Furthermore, lncRNA H19 relative expression levels showed a negative relationship with glomerular filtration rate (GFR) while it was positively correlated with ferritin, phosphorus, parathyroid hormone, TNF-α, IL-6, OC, TAS and TOS levels.
CONCLUSION: lncRNA H19 expressions were increased in CKD stage 3-5 and HD patients, and elevated lncRNA H19 expressions were associated with decreased glomerular filtration rate, inflammation, and mineralization markers in these patients.

Keywords: Chronic kidney disease; IL-6; Oxidative stress; TNF-α; lncRNA H19

DOI: https://doi.org/10.1007/s10157-021-02023-w

Front Oncol. 2020 ;10 622294

LncRNA-Encoded Peptide: Functions and Predicting Methods.

Jiani Xing, Haizhou Liu, Wei Jiang, Lihong Wang.

Long non-coding RNA (lncRNA) was originally defined as the representative of the non-coding RNAs and unable to encode. However, recent reports suggest that some lncRNAs actually contain open reading frames that encode peptides. These coding products play important roles in the pathogenesis of many diseases. Here, we summarize the regulatory pathways of mammalian lncRNA-encoded peptides in influencing muscle function, mRNA stability, gene expression, and so on. We also address the promoting and inhibiting functions of the peptides in different cancers and other diseases. Then we introduce the computational predicting methods and data resources to predict the coding ability of lncRNA. The intention of this review is to provide references for further coding research and contribute to reveal the potential prospects for targeted tumor therapy.

Keywords: Ribo-seq; cancer; long non-coding RNA; peptide; translation

DOI: https://doi.org/10.3389/fonc.2020.622294