bims-lorfki 2021-12-12 papers

Front Cell Dev Biol. 2021 ;9 580754

Long Non-coding RNA ENST00000453774.1 Confers an Inhibitory Effect on Renal Fibrosis by Inhibiting miR-324-3p to Promote NRG1 Expression.

Shumei Tang, Gong Xiao, Qiongjing Yuan, Wei Lin, Xiangning Yuan, Xi Fang, Tianci Deng, Xiangcheng Xiao.

Progressive or chronic renal diseases arise from a process of destructive renal fibrosis. Therefore, the molecular basis of renal fibrosis has attracted increasing attention. In this investigation, we set out to elucidate the potential interaction among long non-coding RNA ENST00000453774.1 (lncRNA 74.1), microRNA-324-3p (miR-324-3p), and NRG1, and to investigate their roles in the context of cellular autophagy and renal fibrosis. We collected 30 renal fibrosis tissue samples for analysis. In other studies, HK-2 cells were stimulated with TGF-β1 to induce a cell model of renal fibrosis, followed by alteration on the expression of lncRNA 74.1, miR-324-3p, or NRG1, or by the addition of AKT activator SC79 in the HK-2 cells. The expression levels of lncRNA 74.1, miR-324-3p, NRG1, autophagy-related proteins (ATG5, ATG7, LC3II/I, and P62), and the corresponding fibrosis markers (Collagen I, Fibronectin, and α-SMA) were subsequently determined using various assay methods. In addition, the proportion of LC3 positive cells and number of autophagosomes were recorded. Results revealed that lncRNA 74.1 and NRG1 were poorly expressed and miR-324-3p was highly expressed in renal fibrosis tissues and modeled cells. LncRNA 74.1 could bind to miR-324-3p, which led to upregulated NRG1 expression and inhibition of the PI3K/AKT signaling pathway. Meanwhile, overexpression of lncRNA 74.1 or down-regulation of miR-324-3p increased the levels of ATG5, ATG7, LC3II, and LC3I, and decreased levels of P62, Collagen I, Fibronectin, and α-SMA, accompanied by elevated proportions of LC3 positive cells and autophagosomes. Findings concur in showing that lncRNA 74.1 could induce cellular autophagy and alleviate renal fibrosis by regulating the miR-324-3p-mediated NRG1/PI3K/AKT axis. This axis may thus present a potential molecular target in renal fibrosis treatment.

Keywords: NRG1; PI3K/AKT signaling pathway; autophagy; long non-coding RNA ENST00000453774.1; microRNA-324-3p; renal fibrosis

DOI: https://doi.org/10.3389/fcell.2021.580754

Expert Rev Mol Diagn. 2021 Dec 06. 1-10

A computational prognostic model of lncRNA signature for clear cell renal cell carcinoma with genome instability.

Tingting Cui, Jiantao Guo, Zhixia Sun.

Long non-coding RNAs (lncRNAs) play a critical role in genomic instability and prognosis of cancer patients, but the methods to identify genomic instability-related lncRNAs have yet to be established. In the present study, to assess the prognostic value of lncRNAs associated with genomic instability in clear cell renal cell carcinoma (ccRCC).A computational framework was established based on the mutation hypothesis and combined lncRNA expression and somatic mutation profiles of the ccRCC genome. Furthermore, a prognostic model was developed using the genome instability-derived lncRNA signature GILncSig based on three lncRNA genes (LINC02471, LINC01234, and LINC00460) and verified using multiple independent patient cohorts.This study established an effective computational method to study the role of lncRNAs in genomic instability, with potential applications in identifying new genomic instability-related cancer biomarkers.

Keywords: Genomic instability; cancer biomarkers; clear cell renal cell carcinoma; computer identification; lncRNA

DOI: https://doi.org/10.1080/14737159.2021.1979960

Neoplasma. 2021 Dec 10. pii: 210823N1206. [Epub ahead of print]

Blocking stanniocalcin 2 reduces sunitinib resistance in clear cell renal cell carcinoma.

Zhen-Qian Qin, Kong-Dong Li, He-Zhen Chu, Xue-Feng Yuan, Hai-Feng Shi, Jie Gu, Yi-Min Xie.

Stanniocalcin 2 (STC2) has been identified as a prognostic marker in renal cell carcinoma. However, the role of STC2 in renal cell carcinoma is still unclear. In this study, we investigated the relationship between high expression of STC2 and sunitinib resistance in cells and the underlying mechanism. Through GEPIA platform analysis based on the TCGA database, it showed that the expression of STC2 in kidney renal clear cell carcinoma (KIRC) was significantly higher than that in the normal population. Real-time quantitative PCR and western blotting detected significantly higher expression levels of STC2 in clear cell renal cell carcinoma (ccRCC) cells than that in normal renal cells. Enzyme-linked immunosorbent assay (ELISA) determined whether there is a high secretion of STC2 in ccRCC cells. The sunitinib resistance could be significantly reduced by STC2 neutralizing antibody but aggravated by the addition of recombinant human STC2 in ccRCC cells. Sunitinib suppressed STC2 expression and secretion, destroyed lysosomal acidic pH, and accumulated in the cells. However, STC2 neutralizing antibody can reduce the accumulation of sunitinib in cells to improve the inhibitory efficiency of sunitinib on cell proliferation. This study suggested STC2 could serve as a potential novel target for the treatment of ccRCC, anti-STC2 antibody might be an option of immunotherapy in the future.

DOI: https://doi.org/10.4149/neo_2021_210823N1206

Int J Mol Sci. 2021 Dec 04. pii: 13126. [Epub ahead of print]22(23):

Nucleolar Proteins and Non-Coding RNAs: Roles in Renal Cancer.

Piotr Popławski, Joanna Bogusławska, Karolina Hanusek, Agnieszka Piekiełko-Witkowska.

Renal cell cancer is the most frequent kidney malignancy. Most RCC cases are classified as clear cell renal cell carcinoma (ccRCC), characterized by high aggressiveness and poor prognosis for patients. ccRCC aggressiveness is defined by classification systems based on changes in morphology of nucleoli, the membraneless substructures of nuclei. The latter act as the sites of ribosome biogenesis as well as the hubs that trap and immobilize proteins, preventing their action in other cellular compartments. Thereby, nucleoli control cellular functioning and homeostasis. Nucleoli are also the sites of activity of multiple noncoding RNAs, including snoRNAs, IGS RNA, and miRNAs. Recent years have brought several remarkable discoveries regarding the role of nucleolar non-coding RNAs, in particular snoRNAs, in ccRCC. The expression of snoRNAs is largely dysregulated in ccRCC tumors. snoRNAs, such as SNHG1, SNHG4 and SNHG12, act as miRNA sponges, leading to aberrant expression of oncogenes and tumor suppressors, and directly contributing to ccRCC development and progression. snoRNAs can also act without affecting miRNA functioning, by altering the expression of key oncogenic proteins such as HIF1A. snoRNAs are also potentially useful biomarkers of ccRCC progression. Here, we comprehensively discuss the role of nucleolar proteins and non-coding RNAs in ccRCC.

Keywords: AluRNA; RCC; lncRNA; microRNA; nucleolus; rRNA; renal cancer; renal cell carcinoma; ribosome biogenesis; snoRNA

DOI: https://doi.org/10.3390/ijms222313126

Horm Metab Res. 2021 Dec;53(12): 818-824

Long Non-Coding RNA Small Nucleolar RNA Host Gene 5 (SNHG5) Regulates Renal Tubular Damage in Diabetic Nephropathy via Targeting MiR-26a-5p.

Qing Cai, Chao Wang, Li Huang, Chen Wu, BingChao Yan, Ting Chen, Qinjun Li, Ling Wang.

The study explored the diagnostic value of SNHG5 in diabetic nephropathy (DN) and investigated the role and mechanism on DN via establishing the in vitro HK2 cell model. This study recruited 62 types 2 diabetes mellitus (T2DM) patients, 58 DN patients and 60 healthy controls (HC). The expressions of serum SNHG5 and miR-26a-5p were measured by RT-qPCR analysis. The diagnostic value of SNHG5 in DN was assessed by ROC curve. The in vitro cell model was built to estimate the effects of SNHG5 on cell viability, cell apoptosis, inflammation response and oxidative stress. Serum SNHG5 was increased in DN patients (relative expression: 2.04±0.34) and had the diagnostic value in DN. After HK2 cells were treated with high glucose, the cell viability decreased and apoptosis increased, and the production of inflammatory cytokines and ROS enhanced significantly. It was noticed that inhibition of SNHG5 could reverse the above phenomenon caused by high glucose. Besides, serum miR-26a-5p was diminished in DN patients, and luciferase reporter gene revealed that miR-26a-5p is direct target of SNHG5. These results indicated that inhibition of SNHG5 may mitigate HG-induced renal tubular damage via targeting miR-26a-5p, which providing a new insight into the mechanism of renal tubule damage in DN patients.

DOI: https://doi.org/10.1055/a-1678-6556