Roles of long non-coding RNAs in colorectal cancer tumorigenesis: A Review

Siddiqui, Halima; Al‐Ghafari, Ayat B.; Choudhry, Hani; Doghaither, Huda A. Al

doi:10.3892/mco.2019.1872

Cited by 35 publications

(31 citation statements)

References 60 publications

(84 reference statements)

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“…Only 1-2% of the human genome encodes proteins whereas 70-90% is transcribed into non-coding RNA (ncRNA) [58,59]. The role of non-coding RNAs in organisms comprises numerous biological functions such as RNA splicing, regulation of transcription and translation, epigenetic modification, cell metabolism, interaction with RNA, DNA, and proteins [60]. Recently, it has been documented their involvement in a several diseases, especially in cancer.…”

Section: Long Non-coding Rnas (Lncrnas)mentioning

confidence: 99%

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Colorectal Adenomas—Genetics and Searching for New Molecular Screening Biomarkers

Siskova

Červená

Král

et al. 2020

IJMS

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Colorectal cancer (CRC) is a malignant disease with an incidence of over 1.8 million new cases per year worldwide. CRC outcome is closely related to the respective stage of CRC and is more favorable at less advanced stages. Detection of early colorectal adenomas is the key to survival. In spite of implemented screening programs showing efficiency in the detection of early precancerous lesions and CRC in asymptomatic patients, a significant number of patients are still diagnosed in advanced stages. Research on CRC accomplished during the last decade has improved our understanding of the etiology and development of colorectal adenomas and revealed weaknesses in the general approach to their detection and elimination. Recent studies seek to find a reliable non-invasive biomarker detectable even in the blood. New candidate biomarkers could be selected on the basis of so-called liquid biopsy, such as long non-coding RNA, microRNA, circulating cell-free DNA, circulating tumor cells, and inflammatory factors released from the adenoma into circulation. In this work, we focused on both genetic and epigenetic changes associated with the development of colorectal adenomas into colorectal carcinoma and we also discuss new possible biomarkers that are detectable even in adenomas prior to cancer development.

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Section: Long Non-coding Rnas (Lncrnas)mentioning

confidence: 99%

“…Observations of Xiang et al [65] suggest that CCAT1-L lncRNA is involved in MYC regulation by intra-chromosome looping between the MYC gene promoter and distal upstream enhancer elements that regulate MYC transcription. The up-regulation of lncRNA-CCAT1 is highly abundant in the premalignant stages of CRC [60,66].…”

Section: Long Non-coding Rnas (Lncrnas)mentioning

confidence: 99%

Colorectal Adenomas—Genetics and Searching for New Molecular Screening Biomarkers

Siskova

Červená

Král

et al. 2020

IJMS

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“…Noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue [16][17][18][19]. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas, among which, the mir-224-5p and mir-203a were upregulated.…”

Section: Discussionmentioning

confidence: 91%

Identification of Tumorigenic and Prognostic Biomarkers in Colorectal Cancer Based on microRNA Expression Profiles

Shi

Zhuang

Zhang

et al. 2020

BioMed Research International

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Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.

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“…Convinced lncRNAs connected to apoptotic pathway were previously analyzed in colorectal diseases. However, the main attention of previous studies was limited to one or two lncRNAs [ 40 ]. In this research, for the first time, we could identify putative lncRNAs involved in regulation of intrinsic apoptosis genes by insertion of CRC cases in a genome-wide lncRNA expression analysis.…”

Section: Discussionmentioning

confidence: 99%

Integrative in silico and in vitro transcriptomics analysis revealed new lncRNAs related to intrinsic apoptotic genes in colorectal cancer

et al. 2020

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Background Pathogenesis of colorectal cancer (CRC) is connected to deregulation of apoptosis while the effect of lncRNAs, as critical regulatory molecules, on this pathway is not clear well. The present study aimed to identify differential expression of genes and their related lncRNAs which are significantly associated with intrinsic apoptotic pathway in CRC. Methods The connection between CRC and apoptosis was investigated by literature reviews and the genes were enriched by using Enrichr. At the next step, differential expression of enriched genes were evaluated between normal and tumor populations in data sets and were downloaded from GEO. Then, meta-analysis and probe re-annotation were performed. For lncRNAs selection through the highest expression correlation with each of candidate genes, mRNA-lncRNA interaction of screened genes and all of lncRNAs were visualized using Cytoscape. Identified differential expression genes and lncRNAs were validated using TCGA-COAD and the obtained data were confirmed by in vitro studies in the presence of Ag@Glu-TSC nanoparticle as an apoptotic inducer. Cytotoxicity and apoptosis induction effect of Ag@Glu-TSC on Caco-2 cells was determined via MTT and Annexin V/PI, respectively. The expression of genes and lncRNAs were assayed in presence of mentioned nanoparticle. Finally, the expression level of desired genes and lncRNAs were proven in CRC tissues compared to adjacent normal tissues. Results After detection of 48 genes associated with intrinsic apoptosis in CRC according to literature, Enrichr screened 12 common genes involved in this pathway. Among them, 6 genes including BCL2, BCL2L11, BAD, CASP7, CASP9, and CYCS expression reduced in tumor tissue compared to normal according to meta-analysis studies and RNA-seq TCGA data. Afterwards, association of 8 lncRNAs comprising CDKN2B-AS1, LOC102724156, HAGLR, ABCC13, LOC101929340, LINC00675, FAM120AOS, PDCD4-AS1 with more than 5 candidate genes were identified. In vitro studies revealed that four selected lncRNAs including, CDKN2B-AS1, LOC102724156, HAGLR and FAM120AOS were significantly increased in the presence of in optimum concentration of Ag@Glu/TSC and decreased in tumor tissues versus adjacent normal tissues. Conclusion This study developed a new data mining method to screen differentially expressed lncRNAs which are involved in regulation of intrinsic apoptosis pathway in CRC quickly using published gene expression profiling microarrays. Moreover, we could validate a number of these regulators in the cellular and laboratory disease models.

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Roles of long non-coding RNAs in colorectal cancer tumorigenesis: A Review

Cited by 35 publications

References 60 publications

Colorectal Adenomas—Genetics and Searching for New Molecular Screening Biomarkers

Colorectal Adenomas—Genetics and Searching for New Molecular Screening Biomarkers

Identification of Tumorigenic and Prognostic Biomarkers in Colorectal Cancer Based on microRNA Expression Profiles

Integrative in silico and in vitro transcriptomics analysis revealed new lncRNAs related to intrinsic apoptotic genes in colorectal cancer

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