Abstract
The role of long non-coding RNAs (lncRNAs) in colorectal cancer (CRC) tumorigenesis and metastasis remains poorly characterized. The aim of this study was to identify novel lncRNAs and their functions in CRC progression. Through microarray analysis of paired normal colorectal mucosa (NM), primary tumor (PT), and metastatic lymph node (MLN) tissues, lncRNA and mRNA expression patterns were identified. Further bioinformatic analyses were performed to compare the biological functions of lncRNAs between tumorigenesis and metastasis of CRC, which was further verified by TCGA-COAD and GSE82236. The expression of lncRNA MIR29B2CHG93 in paired CRC tissues was detected in a cohort of CRC patients. The effects of lncRNA MIR29B2CHG93 on proliferation, migration, and invasion were determined by in vitro experiments. We found that tumorigenesis-associated lncRNAs predominantly participated in the regulation of the EMT/P53/PI3K-Akt/KRAS signaling pathway as well as the processes related to cell cycle and cell mitosis, while metastasis-associated lncRNAs mainly regulated blood vessel morphogenesis and immune-related biological processes. Compared to the TCGA and GSE datasets, seven tumorigenesis-associated lncRNAs and eight metastasis-associated lncRNAs were identified. LncRNA MIR29B2CHG93 knockdown remarkably suppressed tumor growth and metastasis in vitro, which acted as a tumor promoter in CRC. The lncRNA MIR29B2CHG93 was significantly upregulated in CRC tissues and was indicator of unfavorable clinical outcome in CRC. These results revealed novel lncRNAs that provide new insights for an in-depth understanding of CRC progression. In particular, this study identified a novel lncRNA MIR29B2CHG93 in CRC progression, which might be a potential biomarker for diagnosis, prognosis and metastasis-prediction in CRC.
Highlights
Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, and approximately 50% of patients with primary disease eventually develop metastatic disease [1]
We found that tumorigenesis-associated long non-coding RNA (lncRNA) predominantly participated in the regulation of the epithelial-mesenchymal transition (EMT)/P53/PI3KAkt/KRAS signaling pathway as well as the processes related to cell cycle and cell mitosis, while metastasisassociated lncRNAs mainly regulated blood vessel morphogenesis and immune-related biological processes
A total of 448 lncRNA transcripts were differentially expressed in the metastatic lymph node (MLN) relative to normal colorectal mucosa (NM), including 333 upregulated transcripts and 115 downregulated transcripts
Summary
Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, and approximately 50% of patients with primary disease eventually develop metastatic disease [1]. It is widely accepted that the development of CRC is a multistage process, from normal mucosal epithelium to a malignant tumor and progresses to metastasis [2]. While the molecular mechanisms of CRC development have primarily focused on protein-coding genes to identify oncogenes and tumor suppressors and the role of microRNAs [3, 4], there is still a lack of studies focusing on lncRNAs in CRC development. LncRNAs are known to have diverse structural and regulatory roles in protecting chromosome integrity, maintaining genomic architecture, X chromosome inactivation, imprinting, transcription, translation, and epigenetic regulation [6].
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