Abstract
Growing evidences illustrated that long non-coding RNAs (lncRNAs) exhibited widespread effects on the progression of human cancers via various mechanisms. Long intergenic non-protein-coding RNA 01446 (LINC01446), a 3484-bp ncRNA, is known to locate at chromosome 7p12.1. However, its biological functions and specific action mechanism in gastric cancer (GC) are still unclear. In our study, LINC01446 was proved to be markedly upregulated in GC tissues relative to the normal tissues, and positively correlated with the poor survival of GC patients. The multivariate Cox regression model showed that LINC01446 functioned as an independent prognostic factor for the survival of GC patients. Functionally, LINC01446 facilitated the proliferation and metastasis of GC cells. Moreover, RNA-seq analysis demonstrated that LINC01446 knockdown primarily regulated the genes relating to the growth and migration of GC. Mechanistically, LINC01446 could widely interact with histone lysine-specific demethylase LSD1 and recruit LSD1 to the Ras-related dexamethasone-induced 1 (RASD1) promoter, thereby suppressing RASD1 transcription. Overall, these findings suggest that LINC01446/LSD1/RASD1 regulatory axis may provide bona fide targets for anti-GC therapies.
Highlights
Gastric cancer (GC), a main factor in causing cancerrelated mortalities all over the world, is one of the most common gastrointestinal malignancies in China[1,2,3]
Subsequent quantitative real-time PCR analysis in our study revealed that LINC01446 expression was much higher in GC tissues than in the normal tissues (Fig. 1h)
Massive evidences indicated that long noncoding RNAs (lncRNAs), once regarded as ‘junk RNA’, played distinct roles in the occurrence and progression of cancers, but the lncRNAs related to GC are still not clear[27,28]
Summary
Gastric cancer (GC), a main factor in causing cancerrelated mortalities all over the world, is one of the most common gastrointestinal malignancies in China[1,2,3]. Until 2015, GC was considered as the second most common cancer following lung cancer in China based on the latest cancer statistic data[1]. Transcriptome studies indicated that more than 70% of human genomes could be transcribed to RNAs, and most of them were non-coding[6]. Some studies on GC action mechanism revealed that long noncoding RNAs (lncRNAs), the epigenetic regulators at transcriptional or posttranscriptional levels, exhibited crucial effects on the proliferation, apoptosis, and metastasis of GC cells, and drug-resistance[7,8,9]. Low expression of LINC01133 suppressed the Official journal of the Cell Death Differentiation Association
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
