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Association study of genetic variation of lncRNA MALAT1 with carcinogenesis of colorectal cancer.

ABSTRACT: Introduction:Colorectal cancer (CRC) remains a major public health concern worldwide. However, the detailed molecular mechanisms of CRC remain poorly understood. Methods:In the current study, we evaluated associations of four genetic variants located in the promoter and gene region of long noncoding RNAs metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) with CRC susceptibility among a Chinese population with 966 CRC cases and 988 healthy controls, using a two-stage, case-control study design (400 CRC cases and 400 controls in stage 1, and 566 CRC cases and 588 controls in stage 2). Results:We found that the minor alleles of rs619586 (OR=0.73; 95% CI=0.60-0.88; P=0.001) and rs1194338 (OR=0.80; 95% CI=0.70-0.92; P=0.001) were significantly associated with decreased CRC susceptibility. Compared with those with rs619586 -AA genotype, the risk of CRC was significantly lower in individuals with AG genotype (OR=0.76; 95% CI=0.61-0.95) and GG genotype (OR=0.46; 95% CI=0.23-0.90). Compared with those with rs1194338 -CC genotype, the risk of CRC was significantly lower in individuals with AC genotype (OR=0.79; 95% CI=0.65-0.95) and AA genotype (OR=0.68; 95% CI=0.51-0.89). Conclusion:Taken together, our findings provided strong evidence for the hypothesis that genetic variants in lncRNA MALAT1 might contribute to the carcinogenesis of CRC.

SUBMITTER: Zhao K

PROVIDER: S-EPMC6260139 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Association study of genetic variation of lncRNA MALAT1 with carcinogenesis of colorectal cancer.

Zhao Kexin K Jin Si S Wei Bo B Cao Shiqiong S Xiong Zhifan Z

Cancer management and research 20181123

<h4>Introduction</h4>Colorectal cancer (CRC) remains a major public health concern worldwide. However, the detailed molecular mechanisms of CRC remain poorly understood.<h4>Methods</h4>In the current study, we evaluated associations of four genetic variants located in the promoter and gene region of long noncoding RNAs metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) with CRC susceptibility among a Chinese population with 966 CRC cases and 988 healthy controls, using a two- ...[more]

PMID: 30538572

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Project description:BackgroundPreviously, long non-coding RNA (lncRNA) gene AP001469.3 was reported to participate in the construction of an immune-related lncRNA signature, which showed promising clinical predictive value in colorectal cancer (CRC) patients. However, the clinical and immunological significance and biological function of AP001469.3 in CRC remain unclear. In this study, we aim to explore the roles of AP001469.3 in CRC progression, thereby opening an avenue for CRC treatment.MethodsOur study collected data from The Cancer Genome Atlas (TCGA) database and investigated the role of AP001469.3 in CRC through bioinformatics analysis. Cell-type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) methods evaluated the immune infiltration. The biological functions of AP001469.3 in CRC were validated by in vitro experiments. Gene set enrichment analysis (GSEA) was used to estimate the enrichment of functional pathways and gene signatures.ResultsIn this work, high expression of AP001469.3 was found in CRC and was positively associated with tumor-node-metastasis (TNM) stage in CRC. AP001469.3 expression had a strong relationship with microsatellite instability (MSI) in colon adenocarcinoma (COAD). Additionally, AP001469.3 expression was associated with StromalScore, ImmuneScore, ESTIMATEScore, immune cell infiltration (ICI) levels and immune checkpoint (ICP) genes expression in CRC. Subsequent results showed that immunotherapy could be more effective in CRC patients with low-AP001469.3 expression using the immunophenoscore (IPS). We confirmed that the transcript of AP001469.3 gene ENST00000430259 was highly expressed in CRC tissues and cell lines. In vitro experiments indicated that ENST00000430259 knockdown reduced the proliferation, migration and invasion of CRC cells. Finally, our GSEA results showed that the majority of the differentially enriched signaling pathways between the high- and low-AP001469.3 expression groups were immune-related.ConclusionsTaken together, our study demonstrates that lncRNA gene AP001469.3 is associated with immunological characteristics in CRC and promotes malignant progression of CRC. Moreover, AP001469.3 can be potentially used as an immunotherapeutic indicator and a therapeutic target for CRC patients.

Dataset Information

Association study of genetic variation of lncRNA MALAT1 with carcinogenesis of colorectal cancer.

Publications

Association study of genetic variation of lncRNA MALAT1 with carcinogenesis of colorectal cancer.

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