Long Noncoding RNA NEAT1 Impacts Colorectal Cancer Through Modulating MiR-193a-3p/KRAS

As living standard,industry and technology are advancing,colorectal cancer(abbreviated as CRC),the third most common cancer type and the third most dominating cause of cancer-related deaths in the United States,has aroused rising concern because of its high morbidity and mortality.Although the rectal cancer's mobility remains stable in our country,with the changes in Chinese's dietary structure,the mobility of colon cancer has increased during recent years.The formation of CRC is mediated jointly by genetic alterations and non-genetic alterations.Non-genetic factors contain age,gender,high fat intake,obesity,alcohol and deficiency of physical exercise.Among genetic alterations,Kirsten rat sarcoma viral oncogene homolog(abbreviated as KRAS)signaling pathway is one of the most commonly activated,aggravating the occurrence and progression of intestinal neoplasms.The KRAS gene,situating at 12p 12.1,encodes KRAS protein pertaining to the small GTPase superfamily.The normal RAS/PI3K/AKT signaling is adjusted,and cell proliferation,invasion and apoptosis are impacted by anomalous KRAS protein activation.Accordingly,KRAS pertains to an oncogene family to cause cancerous change.In this study,colorectal cancer tissues' KRAS protein level was aberrantly higher than that of adjacent normal tissues.However,the expression of KRAS mRNA in cancer tissues and normal ones didn't show statistical differences,which indicates post-transcriptional regulation.The non-coding RNA regulation is one of the most important post-transcriptional regulations that targeting mRNA.Long noncoding RNA(abbreviated as lncRNAs)are transcripts with in excess of 200 nucleotides(nt)length,whose regulatory functions,e.g.oncogenesis and metastasis,have been specifically investigated since discovery.One of the functions of IncRNAs is to serve as endogenous miRNA sponges in a part of ceRNA network.lncRNA nuclear enriched abundant transcript 1(or nuclear paraspeckle assembly transcript 1,abbreviated as NEAT1)has been identified as a crucial position in varying cancers.NEAT1 is pervasively found higher in human cancers,inclusive of CRC,hepatocellular cancer,breast cancer and lung cancer.High level of NEAT1 bespoke poorer prognosis,but the mechanism of NEAT1 remains elusive.microRNAs(abbreviated as miRNAs)are small noncoding RNAs with 19-22 nt length that typically decrease the stability and translation of messenger RNAs(abbreviated as rmRNAs)through targeting the 3' untranslated region(abbreviated as 3'UTR)of mRNAs.miRNAs are critical for cell functions,e.g.cell cycle,proliferation and invasion.As the lncRNA downstream predicting tools matures,we chose miRNA as the target of lncRNA,with further study between miRNA and mRNA,and found the joint pathway of non-coding RNAs and mRNA as well as proteins.This study found that CRC tissues were remarkably higher in NEAT1 level and KRAS protein expression,whereas with decreased miR-193a-3p level,which bespoke that NEAT1 circuitously regulates KRAS level through miR-193a-3p.We adequately drew upon 2 bioinformatics algorithms and uncovered two direct control of NEAT1/miR-193a-3p and miR-193a-3p/KRAS.Additionally,the role of NEAT1 in controlling miR-193a-3p and KRAS was studied here with small interfering RNA and antisense oligonucleotides both in vitro and in vivo.Meantime,NEAT1 is verified by the foregoing findings as a miR-193a-3p upstream lncRNA with a fundamental role in KRAS modulation,providing novel insight into the lncRNA-based oncological therapeutic approach to treat human colorectal cancer.