Metastasis-associated lung adenocarcinoma transcript 1 molecular mechanisms in gastric cancer progression

Abstract

Gastric cancer (GC) remains among the most common cancers worldwide with a high mortality-to-incidence ratio. Accumulated evidence suggests that long noncoding RNAs (lncRNAs) are involved in gastric carcinogenesis. These transcripts are longer than 200 nucleotides and modulate gene expression at multiple molecular levels, inducing or inhibiting biological processes and diseases. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the best-studied lncRNAs with comprehensive actions contributing to cancer progression. This lncRNA regulates gene expression at the transcriptional and posttranscriptional levels through interactions with microRNAs and proteins. In the present review, we discussed the molecular mechanism of MALAT1 and summarized the current knowledge of its expression in GC. Moreover, we highlighted the potential use of MALAT1 as a biomarker, including liquid biopsy.

Keywords: Gastric carcinogenesis; Liquid biopsy; Long noncoding RNA; Posttranscriptional levels; Prognostic biomarker; Transcriptional levels.

Figure 1

Metastasis-associated lung adenocarcinoma transcript 1 subcellular location. A: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is the red strand around the nuclear spots (white spheres), MALAT1 can interact with proteins present in nuclear speckles; B: MALAT1 can interact with serine/arginine proteins to modulate alternative splicing of pre-mRNAs; C: MALAT1 binds with transcriptional enhancer factor transcriptional enhanced factors with TEA/ATTS domain, blocking Yes-associated protein, inhibiting gene transcription. MALAT1: Metastasis-associated lung adenocarcinoma transcript 1; SR: Serine/arginine-rich; TEAD: Transcriptional enhanced factors with TEA/ATTS domain; YAP: Yes-associated protein.

Figure 2

Metastasis-associated lung adenocarcinoma transcript 1 expression is influenced by protein CCL21. Metastasis-associated lung adenocarcinoma transcript 1 sponges miR-202-3p, then SRSF1 mRNA (serine and arginine-rich splicing factor 1) is translated in protein and activates mammalian target of rapamycin pathway improving epithelial-mesenchymal transition (EMT) factors and decreasing E-cadherin expression. EMT: epithelial-mesenchymal transition; MALAT1: Metastasis-associated lung adenocarcinoma transcript 1; SRSF1: serine and arginine-rich splicing factor 1; mTOR: Mammalian target of rapamycin.

Figure 3

MALAT1 modulates acetylation in promoter region epidermal growth factor-like domain-containing protein 7 located in histone H3. A: Transfection of small interfering MALAT1 reduces acetylation on promoter region of EGFL7 gene (Epidermal growth factor-like domain-containing protein 7), decreasing metastasis, cell invasion and migration; B: Plasmid cloning DNA-MALAT1 transfection increases EGFL7 acetylation and protein expression, promoting migration, invasion, and metastasis of GC cells. EGFL7: Epidermal growth factor-like domain-containing protein 7; MALAT1: Metastasis-associated lung adenocarcinoma transcript 1; siMALAT1: Small interfering RNA MALAT1; pcDNA-MALAT1: Plasmid cloning DNA-MALAT1; siEGFL7: Small interfering RNA EGFL7.