Ruipeng Liang, Zhili Liu, Bo Li, Debing Xiang, Chunrong Wu
{"title":"Regulation of Metastasis and Growth of Colorectal Cancer <i>via</i> Targeting the PTEN Pathway: An Update on the Progress of LncRNA MLLT4-AS1.","authors":"Ruipeng Liang, Zhili Liu, Bo Li, Debing Xiang, Chunrong Wu","doi":"10.2174/0115748928299796240523075219","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>This study aimed to identify the expression and the clinical significance of lncRNA MLLT4-AS1 in CRC.</p><p><strong>Methods: </strong>The level of MLLT4-AS1 in CRC was evaluated <i>via</i> 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 <i>in vivo</i> impact of MLLT4-AS1 plasmids on tumor growth. RNA pull-down analysis was used to search for possible targets of MLLT4-AS1.</p><p><strong>Results: </strong>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 <i>in vivo</i> 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.</p><p><strong>Conclusion: </strong>The study concluded that the MLLT4-AS1/PTEN axis may represent an innovative therapeutic intervention for CRC patients.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"634-647"},"PeriodicalIF":4.1000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Recent patents on anti-cancer drug discovery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0115748928299796240523075219","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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.
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