Regulation of Metastasis and Growth of Colorectal Cancer via Targeting the PTEN Pathway: An Update on the Progress of LncRNA MLLT4-AS1.

Abstract

Background: Globally, colorectal cancer (CRC) is known as the primary cause of mortality. Recent studies have reported that long non-coding RNAs (lncRNAs) are essential in assessing the survival of CRC patients. However, the function of the novel lncRNA MLLT4-AS1 in CRC is still unknown.

Objective: This study aimed to identify the expression and the clinical significance of lncRNA MLLT4-AS1 in CRC.

Methods: The level of MLLT4-AS1 in CRC was evaluated via the TCGA database. The relative level of MLLT4-AS1 in CRC cell lines was assessed by RT qPCR analysis. In cell culture, HT29 cells were transfected with MLLT4-AS1 siRNA, negative control, overexpressed MLLT4-AS1, or PTEN plasmids. Flow cytometry, CCK 8 assay, wound healing analysis, and transwell assay were used to quantify apoptosis, cell propagation, migration, and invasion, respectively. A nude mouse xenograft model was developed to evaluate the in vivo impact of MLLT4-AS1 plasmids on tumor growth. RNA pull-down analysis was used to search for possible targets of MLLT4-AS1.

Results: MLLT4-AS1 was substantially increased in CRC cell lines and patients. It inhibited CRC cell apoptosis and accelerated their proliferative, migration, and invasive properties. In in vivo analysis, MLLT4-AS1 also enhanced the metastasis and proliferation of CRC cells. It was found that PTEN was substantially enriched by biotin-labeled PTEN, as identified via an RNA pull-- down analysis. The expression of phosphatase and PTEN was suppressed by MLLT4-AS1 by ubiquitination proteasome-dependent RNA degradation. Thus, PTEN is considered a potential target of MLLT4-AS1. By targeting PTEN, MLLT4-AS1 intensified the biological behavior of malignant CRC.

Conclusion: The study concluded that the MLLT4-AS1/PTEN axis may represent an innovative therapeutic intervention for CRC patients.