RESUMO
BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in different pathogenesis pathways including cancer pathogenesis. The adenoma-carcinoma pathway in colorectal cancer may involve the aberrant and variable gene expression of regulatory RNAs. This study was conducted to analyse the expression and prognosis prediction ability of two natural antisense transcripts, protein kinase C theta antisense RNA 1 (PRKCQ-AS1), and special AT-rich sequence binding protein 1 antisense RNA 1 (SATB1-AS1) in colorectal low-grade adenoma, advanced adenoma, and adenocarcinomas. METHODS: In this study, from two RNA-seq analyses of CCAT1-ko cells and colorectal carcinoma biopsies having diminished and increased levels of CCAT1 transcription, respectively, we nominated two antisense lncRNAs of PRKCQ-AS1 and SATB1-AS1. Samples from colorectal low-grade adenomas, advanced adenomas, adenocarcinomas, and adjacent tissue were subjected to RT-qPCR to determine the expression of PRKCQ-AS1, SATB1-AS1 along with colon cancer-associated transcript 1 (CCAT1) and cMYC. In addition, we used different bioinformatics analyses and webservers (including GEPIA 2, TCGA, and CancerMine) to elucidate the prognosis prediction value, the expression correlation of sense-antisense pair of genes, and the expression profile of these antisense transcripts at the presence or absence of mutations in the driver genes, or the corresponding sense genes. RESULTS: PRKCQ-AS1 showed a wide range of expression levels in colorectal adenoma, advanced adenoma, and adenocarcinoma. Upregulation of PRKCQ-AS1 was related to a significant decrease in survival of colorectal cancer (CRC) patients. The expression levels of PRKCQ-AS1 and PRKCQ were strong and significantly concordant in normal and cancerous colorectal tissues. While SATB1-AS1 showed a wide range of expression in colorectal adenoma, advanced adenoma, and adenocarcinoma as well, its expression was not related to a decrease in survival of CRC patients. The expression levels of SATB1-AS1 and SATB1 (the sense gene) were not strong in normal colorectal tissues. In addition, where SATB1 gene was mutated, the expression of SATB1-AS1 was significantly downregulated. CONCLUSIONS: We found the expression of PRKCQ-AS1 and SATB1-AS1 at a given stage of CRC very variable, and not all biopsy samples showed the increased expression of these antisense transcripts. PRKCQ-AS1 in contrast to SATB1-AS1 showed a significant prognostic value. Since a significantly concordant expression was observed for SATB1-AS1 and SATB1 in only cancerous, and for PRKCQ-AS1 and PRKCQ in both normal and cancerous colorectal tissues, it can be concluded that common mechanisms may regulate the expression of these sense and antisense genes.
RESUMO
Acute myeloid leukemia (AML) represents a hematopoietic cancer with an invasive property. Chemoresistance blunts the therapeutic effect of chemotherapeutics in AML. Long noncoding RNAs (lncRNAs) have been implicated in chemotherapy resistance in AML. Transcriptome sequencing in the current study was applied to clarify the differentially expressed lncRNAs between peripheral blood mononuclear cells of AML and normal samples. The expression of special AT-rich sequence binding protein 1 antisense RNA 1 (SATB1-AS1) and 2'-5'-oligoadenylate synthetase 2 (OAS2) in AML patients was evaluated by qRT-PCR. The relationships among SATB1-AS1, microRNA-580 (miR-580) and OAS2 were investigated by dual-luciferase reporter assay. We observed that SATB1-AS1 and OAS2 were upregulated, while miR-580 was downregulated in AML patients. SATB1-AS1 depletion suppressed proliferation, and enhanced apoptosis and sensitivity of AML cells. Additionally, SATB1-AS1 promoted the expression of OAS2 by acting as a molecular sponge of miR-580 in AML. miR-580 downregulation, OAS2 overexpression and a selective glycogen synthase kinase (GSK)-3ß inhibitor AR-A014418 abolished the effects of SATB1-AS1 deletion on the chemosensitivity of AML cells. In conclusion, SATB1-AS1 knockdown promotes the sensitivity of AML cells by upregulating miR-580 and downregulating OAS2 through the GSK3ß/ß-catenin pathway, providing new insights into the function of SATB1-AS1 as a miRNA sponge in AML.