Long non-coding RNA ABHD11-AS1 promotes colorectal cancer progression and invasion through targeting the integrin subunit alpha 5/focal adhesion kinase/phosphoinositide 3 kinase/Akt signaling pathway.

Long non-coding (lnc)RNA ABHD11-AS1 participates in the development and progress of various cancers, but its role in colorectal cancer (CRC) remains poorly known. In the present study, public database analysis and quantitative reverse transcription PCR of CRC and normal tissues showed that ABHD11-AS1 was overexpressed in CRC and associated with poor prognosis in CRC patients. Both in vitro and in vivo experiments demonstrated that loss-of-function of ABHD11-AS1 attenuated the proliferation, migration, and invasion of CRC cells and induced their apoptosis. Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the phosphoinositide 3 kinase (PI3K)/Akt signaling pathway is a potential target of ABHD11-AS1. Additionally, we noted that ABHD11-AS1 deficiency reduced integrin subunit alpha (ITGA)5 expression, and impaired the phosphorylation of P85, focal adhesion kinase (FAK), and Akt1 in CRC cell lines and tumor tissues of nude mice. Furthermore, we observed that ITGA5 overexpression abrogated the effect of ABHD11-AS1 knockdown on the proliferation and invasion abilities of CRC cells. Taken together, our studies suggest that lncRNA ABHD11-AS1 promotes proliferation, migration, and invasion in CRC by activating the ITGA5/Fak/PI3K/Akt signaling pathway, and that the ITGA5/Fak/PI3K/Akt axis is a promising target for CRC therapy.

Downregulation of LncRNA-RP11-317J10.2 promotes cell proliferation and invasion and predicts poor prognosis in colorectal cancer.

OBJECTIVES: Using microarray analysis, we previously showed that many lncRNAs are differentially expressed in colorectal cancer (CRC) tissues compared with normal tissues, suggesting that lncRNAs may be involved the initiation and progression of CRC. In this study, we investigated the expression and function of lncRNA-RP11-317J10.2 in human CRC tissues and cell lines. METHODS: LncRNA-RP11-317J10.2 expression level was analyzed in 52 colon cancer and cell lines. We used shRNA to knock-down the expression of RP11-317J10.2, and then proliferation assay, colony formation assay, Boyden chamber assay, FACS and Kaplan-Meier survival analysis were performed to explore the biological effect of RP11-317J10.2. Cyclin D1 protein level was detected by Western blot. RESULTS: LncRNA-RP11-317J10.2 is downregulated in CRC and decreased expression is significantly associated with advanced tumor stage, larger tumor size and poor prognosis. RNA interference-mediated knockdown of lncRNA-RP11-317J10.2 in CRC cells promotes G1-to-S cell cycle transition, enhances invasiveness and facilitates cell growth in vitro and in mouse tumor xenograft models. Cyclin D1 was upregulated by lncRNA-RP11-317J10.2 knockdown, and co-expression of cyclin D1-targeting siRNA abrogates the pro-tumorigenic effects of lncRNA-RP11-317J10.2 knockdown. CONCLUSIONS: This study reveals a crucial role for lncRNA-RP11-317J10.2 in CRC growth and invasion via upregulation of cyclin D1 expression and suggests that expression of this lncRNA may be a potential prognostic biomarker for CRC.

Expression profile of long non-coding RNAs in colorectal cancer: A microarray analysis.

Colorectal cancer (CRC) is one of the most prevalent malignant tumors and the second cause of cancer-related mortality worldwide. Due to increased morbidity and mortality rates, there is an urgent need to understand the pathogenesis of CRC, discover strategies that can improve diagnosis, and ultimately identify therapies targeting this disease. Over the past several years, research into tumor progression mechanisms has been devoted to identifying and understanding various coding and non-coding regions of the genome and how these genetic variants may affect tumorigenesis and progression. Recently, long non-coding RNAs (lncRNAs), which are non­protein coding transcripts longer than 200 nucleotides, have emerged as a key aspect in tumor pathogenesis. In the present study, we examined the lncRNA and mRNA expression profiles in 4 patients with colon adenocarcinoma, with paired adjacent normal tissues as controls. Microarray data showed that a total of 3,523 lncRNAs and 2,515 mRNAs were consistently differentially expressed in the CRC tissues compared to adjacent normal tissues. Upon comparison of the differentially expressed transcripts between the groups, we identified 22 pathways which were related to the upregulated transcripts and 24 pathways that corresponded to the downregulated transcripts. Gene ontology analysis revealed that the upregulated transcripts were predominantly enriched in DNA metabolic processes, and the downregulated transcripts were predominantly enriched in organic hydroxyl compound metabolic processes. Coding-non-coding gene co-expression analysis showed that these differentially expressed lncRNAs were closely correlated with 'Wnt signaling pathway' components, whose aberrant activation plays a central role in CRC, indicating that a functional correlation exists between them. In conclusion, the results of the microarray and informatic analysis strongly suggest that lncRNA dysregulation is involved in the complicated process of CRC development, and may represent a novel class of diagnostic markers or therapeutic targets for CRC.