Long Noncoding RNA Linc02023 Regulates PTEN Stability And Suppresses Tumorigenesis Of Colorectal Cancer In A PTEN-dependent Pathway

Colorectal cancer(CRC)is the third most common cancer worldwide,with 1.4 million new cancer cases diagnosed and 690 thousand deaths occurring worldwide annually.The development of CRC is believed to be associated with cigarette smoking,excess body weight,an unhealthy diet,and physical inactivity.However,the molecular mechanisms underlying the occurrence and development of CRC remain to be investigated,which may contribute to the diagnosis and treatment of CRC.Long noncoding RNAs(lncRNAs)are defined as a class of nonprotein-coding transcripts composed of more than 200 nucleotides,which was considered as junk RNA.LncRNAs can be classified as enhancer RNAs(eRNAs),and sense and antisense transcripts based on their relationship with the nearest protein-coding transcripts.LncRNAs are crucial in the transformed phenotype of cancer cells in correlation with distinct gene sets that influence cell cycle regulation,survival,immune response,or differentiation because of their tissue-specific expression and regulation of gene expression via diverse mechanisms.The mechanisms of lncRNAs include gene regulation in cis/trans,organization of nuclear architecture,and regulation of interacting proteins and RNAs.For example,lncRNA EPIC1 promotes tumorigenesis and regulates cell cycle progression in breast cancer by directly interacting with MYC and influencing its target genes.PTEN,a multidomain protein,was first identified as a tumor suppressor by three groups in 1997.Studies on human samples and mouse models show that loss of PTEN function alone is sufficient to cause cancer in certain tissues,and reduction of PTEN more than 50% promotes cancer progression.PTEN suppresses cell proliferation by exerting a negative influence on PI3K/AKT pathway in the cytoplasm,regulating cell cycle proteins and stability and transcriptional activity of P53.Although many mechanisms of transcriptional and posttranscriptional regulation of the expression of PTEN are clear,including epigenetic silencing,transcriptional regulation,regulation by miRNAs and disruption of ceRNAs networks,posttranslational modifications(PTMs),PTEN-interacting proteins,dimerization,and secretion,the relationship between lncRNAs and PTEN remains unexplored.This study aims to investigate the transcriptomic associations between lncRNAs and mRNAs in patients with CRC.An aberrant downregulation Linc02023 is identified as a tumor suppressor,and the underlying mechanisms are examined.The results elucidate that Linc02023 is a PTEN-interacting RNA,maintaining its stability and restoring its activity,thus suppressing the progression of CRC.