Abstract
BackgroundLong non-coding RNAs (lncRNAs), a class of non-coding RNAs (ncRNAs) associated with diverse biological processes of cells. Over the past decades, cumulating research evidences revealed that abnormal expressions of lncRNAs are associated with colorectal cancer (CRC) initiation, progression, metastasis, and resistance to therapies. Moreover, their usefulness as candidate biomarkers for CRC diagnosis and prognosis are well evident throughout previous literature. In the current study, we examined the role and molecular mechanisms of newly identified lncRNA named RNA associated with metastasis-11 (RAMS11) in CRC development.MethodsThe expression of RAMS11 in CRC cell lines DLD-1, HT-29, HCT-116, and SW480 and colon normal cells CCD-112-CoN were evaluated by quantitative RT-qPCR. The results showed that the RAMS11 is significantly upregulated in CRC cell lines compared to the normal cells. The CCK-8 proliferation assay, colony formation assay, and migration assay were performed to evaluate the biological and physiological functions of RAMS11 in vitro. To decipher the molecular mechanisms of RAMS11 medicated CRC progression, we further performed western blot analysis of the key pathway proteins (e.g., AMPK, AKT, and mTOR).ResultsOur results revealed that higher expression of RAMS11 is associated with increased CRC proliferation, migration, and development of metastasis. Knockdown of RAMS11 induced autophagy, apoptosis along with reduction of epithelial-mesenchymal transition (EMT) suggesting that RAMS11 is involved in CRC progression. The molecular mechanisms of RAMS11 indicated that knockdown of RAMS11 significantly inhibited CRC carcinogenesis through mTOR-dependent autophagy induction.ConclusionsIn sum, our results suggested that RAMS11 is an important oncogene in CRC pathogenesis. Targeting RAMS11 could be a potential therapeutic strategy for CRC management.
Highlights
Long non-coding RNAs, a class of non-coding RNAs associated with diverse biological processes of cells
RNA associated with metastasis-11 (RAMS11) is a newly identified Long non-coding RNAs (lncRNAs) which was firstly identified by Dr Maher’s Lab [18]
RAMS11 is highly overexpressed in colorectal cancer (CRC) cell lines and can be downregulated by Dicer‐substrate siRNA techniques The expression of RAMS11 was confirmed in CRC cell lines (DLD-1, HT-29, HCT-116, and SW480) and normal colon cells CCD-112CoN by RT-qPCR as shown in Downregulation of RAMS11 inhibited cell proliferation, colony formation and migration of CRC cells To understand the functional roles of RAMS11 in CRC proliferation, growth, and migration, we performed Cell counting kit-8 (CCK-8) cell proliferation assay, colony formation assay, and migration assay
Summary
Long non-coding RNAs (lncRNAs), a class of non-coding RNAs (ncRNAs) associated with diverse biological processes of cells. Over the past decades, cumulating research evidences revealed that abnormal expressions of lncRNAs are associated with colorectal cancer (CRC) initiation, progression, metastasis, and resistance to therapies. Their usefulness as candidate biomarkers for CRC diagnosis and prognosis are well evident throughout previous literature. We examined the role and molecular mechanisms of newly identified lncRNA named RNA associated with metastasis-11 (RAMS11) in CRC development. Colorectal cancer (CRC) has been ranked as the third most diagnosed malignancy and the second leading cause of cancer-related death by The Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN) statistics in. The search for a potential biomarkers and therapeutic targets for CRC diagnosis and prognosis may be useful for identifying individuals at risk of developing CRC or to hasten the diagnosis of early CRC for better treatment outcome
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