Downregulation of the lncRNA ASB16-AS1 Decreases LARP1 Expression and Promotes Clear Cell Renal Cell Carcinoma Progression via miR-185-5p/miR-214-3p

Abstract

Clear cell renal cell carcinoma (ccRCC) comprises approximately 75% of renal cell carcinomas, which is one of the most common and lethal urologic cancers, with poor quality of life for patients and is a huge economic burden to health care systems. It is imperative we find novel prognostic and therapeutic targets for ccRCC clinical intervention. In this study, we found that the expression of the long noncoding RNA (lncRNA) ASB16-AS1 was downregulated in ccRCC tissues compared with non-diseased tissues and was also associated with advanced tumor stage and larger tumors. By constructing cell and mouse models, it was found that downregulated lncRNA ASB16-AS1 enhanced cell proliferation, migration, invasion, and promoted tumor growth and metastasis. Furthermore, by performing bioinformatics analysis, biotinylated RNA pull-downs, AGO2-RIP, and luciferase reporter assays, our findings showed that downregulated ASB16-AS1 decreased La-related protein 1 (LARP1) expression by inhibiting miR-185-5p and miR-214-3p. Furthermore, it was found that overexpression of LARP1 reversed the promotive effects of downregulated ASB16-AS1 on ccRCC cellular progression. Our results revealed that downregulated ASB16-AS1 promotes ccRCC progression via a miR-185-5p-miR-214-3p-LARP1 pathway. We suggest that this pathway could be used to monitor prognosis and presents therapeutic targets for ccRCC clinical management.

Protein co-expression network-based profiles revealed from laser-microdissected cancerous cells of lung squamous-cell carcinomas

“…Significant upregulated LARP1 was frequently reported to correlate with adverse prognosis in several cancers including NSCLC 48 . In contrast, clear cell renal cell carcinoma progression was promoted by decreased LARP1 derived from the downregulation of the long noncoding RNA ASB16-AS1 by inhibiting miR-185-5p and miR-214-3p 49 . Our result should be understood along contexts underpinning disease mechanisms and because the function of LARP1 is highly controversial 50 .…”

Comprehensive analysis of 7-methylguanosine and immune microenvironment characteristics in clear cell renal cell carcinomas

“…EIF4E1B is associated with eukaryotic canonical translation initiation; most eukaryotes have distinct EIF4E subgenes ( Ying et al, 2021 ). LARP1 is involved in cell growth and proliferation, and its overexpression may reverse the progression of ccRCC [( Tcherkezian et al, 2014 ), ( Li et al, 2020 )]. GEMIN5 affects the assembly of motor neuron complexes; GEMIN5 mutations can shorten the life span of patients and affect movement and development ( Kour et al, 2021 ).…”

Protein Co-expression Network-based Profiles Revealed from Laser-microdissected Cancerous Cells of Lung Squamous-Cell Carcinomas

“…In contrast, clear cell renal cell carcinoma progression was promoted by decreased LARP1 derived from the downregulation of the long noncoding RNA ASB16-AS1 by inhibiting miR-185-5p and miR-214-3p [49]. Our result should be understood along contexts underpinning disease mechanisms and because the function of LARP1 is highly controversial [50]. The highly activated MYC, MLXIPL, and MYCN and highly suppressed LARP1 and RICTOR were predicted for the WM28 module.…”