Research Paper Volume 13, Issue 24 pp 25859—25885

Identification and functional analysis of lncRNAs and mRNAs between tumorigenesis and metastasis in CRC

Hongtao Liu1, *, , Yuan Tian2, *, , Jiaxi Li1, *, , Guoxia Zhang1, , Qun Liu1, , Min Yang1, , Longtao Yue1, , Qiwei Cao1, , Guihui Zhang1, , Yuxia Cheng1, , Na Kong1, , Lei Fang1, , Shoupeng Li1, , Qing Sun1, ,

  • 1 Department of Pathology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Clinical Pathology, Shandong Lung Cancer Institute, Shandong Institute of Nephrology, Jinan 250014, Shandong, P.R. China
  • 2 Somatic Radiotherapy Department, Shandong Second Provincial General Hospital, Shandong Provincial ENT Hospital, Huaiyin, Jinan 250023, Shandong, P.R. China
* Equal contribution

Received: September 1, 2021       Accepted: November 24, 2021       Published: December 26, 2021      

https://doi.org/10.18632/aging.203775
How to Cite

Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

CRC: colorectal cancer; lncRNA: long non-coding RNA; EMT: epithelial-mesenchymal transition; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; KEGG: Kyoto Encyclopedia of Genes and Genomes; MCODE: Molecular Complex Detection; GO: Gene Oncology; ECM: Extracellular Matrix.