Abstract
BackgroundLong non-coding RNAs (lncRNAs) have been defined as vital regulators in the progression of human cancers, including colorectal cancer (CRC). Long intergenic non-protein coding RNA 667 (LINC00667) is a tumor promoter in several cancer types, while its role in CRC remains to be unmasked. This study focused on exploring the potential function and regulatory mechanism of LINC00667 in CRC.MethodsqRT-PCR analysis was applied to detect the expression of LINC00667 in CRC cells. Loss-of function assays revealed the role of LINC00667 silencing in regulating CRC cell proliferation, apoptosis and migration. In vivo study demonstrated the effect of LINC00667 silencing on CRC cell growth. Mechanism experiments were conducted to determine the upstream or the downstream molecular mechanism of LINC00667 in CRC cells.ResultsLINC00667 was expressed at high level in CRC cells. LINC00667 knockdown significantly inhibited CRC cell growth and migration. YY1 transcription factor induced the upregulation of LINC00667 in CRC cells by transcriptionally activating LINC00667. In addition, miR-449b-5p could interact with LINC00667 in CRC cells. Intriguingly, miR-449b-5p directly targeted to YY1, thus inhibiting YY1 expression. YY1 recovered the CRC cell functions impaired by LINC00667 silencing.ConclusionsLINC00667 is transcriptionally activated by YY1 and promotes cell proliferation and migration in CRC by sponging miR-449b-5p to upregulate YY1.
Highlights
Long non-coding RNAs have been defined as vital regulators in the progression of human cancers, including colorectal cancer (CRC)
LINC00667 was silenced by short hairpin RNAs (shRNAs) targeting LINC00667 in LoVo and HCT116 cells with non-targeting shRNA as negative control
EdU assay showed that EdU-positive cells were decreased in LINC00667ilenced CRC cells compared to control cells (Fig. 1d)
Summary
Long non-coding RNAs (lncRNAs) have been defined as vital regulators in the progression of human cancers, including colorectal cancer (CRC). Long intergenic non-protein coding RNA 667 (LINC00667) is a tumor promoter in several cancer types, while its role in CRC remains to be unmasked. Long noncoding RNA (lncRNA) is a class of non-protein coding transcripts that are longer than 200 nucleotides (nt) [4]. Previous studies have demonstrated that dysregulated lncRNAs have crucial roles in various biological processes, such as cell differentiation, proliferation, apoptosis and migration [5,6,7]. Evidence has been provided to show the functions of lncRNAs in tumorigenesis and malignant development of human cancers. LncRNA MIR205HG functions as a miR122-5p sponge to accelerate tumor growth and progression of cervical cancer [8].
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