SNHG19

Renal cell carcinoma is the most common aggressive tumor of the genitourinary system. The main pathological subtype is clear cell renal cell carcinoma (ccRCC), and its treatment options are very limited. Therefore, identifying specific biomarkers of ccRCC is of great significance for diagnosis and prognosis.

First, we obtained transcriptome data and clinical data of 611 patients with renal clear cell carcinoma to analyze the relationship between hypoxia-related lncRNAs and overall survival (OS). We screened hypoxia-related lncRNAs through Pearson correlation and Cox regression analysis. Univariate and multivariate regression analysis were applied to assess survival-related risk factors. According to the median risk score, patients were divided into two groups. Next, a nomogram map was built, and GSEA was used for gene function annotation. RT-qPCR, Western Blot, and Flow Cytometry were used to determine the role of SNHG19 in RCC cells.

By analyzing the co-expression of hypoxia genes and lncRNAs, 310 hypoxia-related genes were obtained. Four sHRlncRs (AC011445.2, PTOV1-AS2, AP004609.3, and SNHG19) with the highest prognostic values were included in the group to construct the HRRS model. The high-risk group had a shorter OS than the low-risk group. HRRS was considered to be an independent prognostic factor and associated with OS. The two groups showed different pathways in GSEA. Experiments showed that SNHG19 plays essential roles in the autophagy and apoptosis of RCC cells.

We constructed and validated a hypoxia-related lncRNA model for ccRCC patients. This study also provides new biomarkers for the poor prognosis of ccRCC patients.

Hepatoblastoma (HB) is a common pediatric malignant liver tumor that is characterized by a low level of genetic mutations. Alternative splicing (AS) has been shown to be closely associated with cancer progression, especially in tumors with a low mutational burden. However, the role of AS in HB remains unknown.

Transcriptome sequencing was performed on 5 pairs of HB tissues and matched non-tumor tissues to delineate the AS landscape in HB. AS events were validated in 92 samples from 46 patients. RNA pull-down and RNA immunoprecipitation assays were carried out to identify splicing factors that regulate the AS of small nucleolar RNA host genes (SNHG). Patient-derived organoids (PDOs) were established to investigate the role of the splicing factor polyadenylate-binding nuclear protein 1 (PABPN1).

This study uncovered aberrant alternative splicing in HB, including lncRNAs from SNHG family that undergo intron retention in HB. Further investigations revealed that PABPN1, a significantly upregulated RNA binding protein, interacts with splicing machinery in HB, inducing the intron retention of these SNHG RNAs and the downregulation of intronic small nucleolar RNAs (snoRNAs). Functionally, PABPN1 acts as an oncofetal splicing regulator in HB by promoting cell proliferation and DNA damage repair via inducing the intron retention of SNHG19. Knock-down of PABPN1 increases the cisplatin sensitivity of HB PDOs.

Our findings revealed the role of intron retention in regulating snoRNA expression in hepatoblastoma, explained detailed regulatory mechanism between PABPN1 and the intron retention of SNHG RNAs, and provided insight into the development of new HB treatment options.

Aims: In this study, the authors hypothesized that, in an in vitro Alzheimer's disease model, the epigenetic axis of SNHG19/hsa-miR-137 functionally regulates amyloid beta peptide 25-35 (Aβ_25-35)-induced SH-SY5Y cytotoxicity. Methods: Dual luciferase activity assay demonstrated that SNHG19 could directly bind hsa-miR-137. In Aβ_25-35-treated SH-SY5Y cells, SNHG19 was upregulated and hsa-miR-137 downregulated. Results: SNHG19 knockdown ameliorated Aβ_25-35-induced SH-SY5Y cytotoxicity, then reversed by secondary hsa-miR-137 downregulation. TNFAIP1 was dynamically regulated by Aβ_25-35 and gene modifications in SH-SY5Y cells. Finally, upregulation of TNFAIP1 reversed the protective effect of SNHG19 knockdown on Aβ_25-35-induced cytotoxicity. Conclusions: The authors concluded that the epigenetic axis of SNHG19/hsa-miR-137/TNFAIP1 may functionally regulate Aβ_25-35-induced SH-SY5Y cytotoxicity, thus making it a potential molecular target for Alzheimer's disease treatment.