Abstract
The lncRNA MALAT1 has multiple biological functions, including influencing RNA processing, miRNA sponging, and cancer development. It is acknowledged that miR663a and its targets are inflammation-related genes frequently deregulated in many cancers. The associations between MALAT1 and miR663a and their target genes remain unknown. In this study, it was found that in colon cancer (CC) cells, MALAT1 and miR663a were reciprocally repressed in cDNA array screening and qRT-PCR analysis. However, MALAT1 was significantly upregulated in CC tissues, and miR663a was significantly downregulated relative to the corresponding surgical margin (SM) tissues. An inverse relationship between MALAT1 and miR663a expression was detected among CC tissue samples (n = 172, r = −0.333, p < 0.0001). The RNA-pulldown results showed MALAT1 lncRNA–miR663a binding. The results of luciferase-reporter analysis further revealed that the MALAT1 7038–7059 nt fragment was the miR663a seed sequence. Both miR663a knockdown and MALAT1 activation alone significantly upregulated the expression levels of miR663a targets, including TGFB1, PIK3CD, P53, P21, and JUND, in the CC cell lines HCT116 and SW480. A positive relationship was also observed between the expression levels of MALAT1 and these miR663a targets in the above 172 CC samples and 160 CC samples in publicly available databases. In addition, reciprocal abolishment of the effects of miR663a overexpression and MALAT1 activation on the proliferation, migration, and invasion of cancer cells was also observed, while miR663a upregulation and MALAT1 activation alone inhibited and promoted the behaviors of these CC cell lines, respectively. All these suggested that, as a competing endogenous lncRNA, MALAT1 maybe a dominant protector for the degradation of miR663a targets. miR663a and MALAT1 may consist of a negative feedback loop to determine their roles in CC development.
Highlights
In the genomes of mammals, less than 2% of the human genome comprises protein-coding sequences, and 98% comprises non-protein coding regions that may play roles in physiological and pathological processes[1]
These results suggest that MALAT1 may be a miR663a target
MALAT1 upregulation by saR-MALAT1 significantly promoted the proliferation, migration, and Discussion MALAT1, as a component of nuclear paraspeckles, is a well-studied Long noncoding RNAs (lncRNAs) involved in pre-mRNA splicing[22]
Summary
In the genomes of mammals, less than 2% of the human genome comprises protein-coding sequences, and 98% comprises non-protein coding regions that may play roles in physiological and pathological processes[1]. Long noncoding RNAs (lncRNAs) are transcribed from nonprotein coding regions that are longer than 200 nucleotides in length. The metastasis-associated lung adenocarcinoma transcript 1 gene (MALAT1, NEAT2) is the first discovered human tumor-related lncRNA that promotes the progression and metastasis of cancers[3]. MALAT1 is ubiquitously expressed in normal tissues and is frequently upregulated in human cancers[4,5,6,7,8]. It may function as a component of RNA-
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