Pan-Cancer Analysis Of LncRNA PCAT6 And Its Effect On Esophageal Squamous Cell Carcinoma Cell Proliferation And Migration

Background: LncRNA is involved in a variety of biological processes and is a key regulator of human malignant tumour initiation,development and response to treatment.The lncRNA PCAT6 is associated with tumour initiation,progression and poor prognosis.However,its role in pan-cancer and how it relates to thetumour immune microenvironment remains to be elucidated.This study aims to compare the expression characteristics,prognostic value and relationship with tumour immune microenvironment of PCAT6 in pan-cancer.The regulation of PCAT6 in the progression of oesophagealsquamous ccarcinoma(ESCC)has also been under discussion.Objective: To study the expression and prognosis of PCAT6 in 33 different types of tumours and its relationship with theimmune microenvironment of the tumour.To clarify the expression of PCAT6 in esophageal cancer(ESCA)and its prognostic relationship;to identify the signalling pathway that is involved in PCAT6;to investigate how PCAT6 expression affects ESCC proliferation,invasion,migration and stemness;to study the regulatory effect of PCAT6 on JAK/STAT signalling pathway.To illuminate the molecular mechanism of PCAT6,whichaffects the progression and occurrence of ESCC through theregulation of the JAK/STAT signalling pathway.Methods: The pan-cancer dataset was downloaded from the UCSC database to analyse the relationship between PCAT6 expression in different tumour tissues and patient prognosis,clinical characteristics(TNM stage,pathological stage,pathological grade,gender,and age),immune infiltration,tumour microenvironment,microsatellite instability,immune neoantigen,DNA mismatch repair and methyltransferase.To determine the expression of PCAT6 in ESCA,gene expression data for ESCA were extracted from the TCGA database.Gene expression data of GSE100942 chip(GPL570)was downloaded from GEO database to verify the expression of PCAT6 in ESCA.Kaplan-Meier database was used to analyse the relationship between the prognosis of ESCA patients and the expression of PCAT6.The PCAT6 signalling pathway was identified by GSEA enrichment analysis.ESCC cell biology functional changes using CCK8 proliferation,aggregation formation,scarring,transwell invasion,and migration experiment conducted research.Changes in the expression levels of cancer stem cell related genes(SOX2,SOX9,OCT4,and NANOG)and JAK/STAT pathway related genes(JAK2,p-JAK2,STAT3,pSTAT3,and CCND1)were investigated by RT-q PCR and Western blot after knockdown of PCAT6 in ESCC EC109 cells.Results:1.PCAT6 is significantly upregulated in many tumour tissues and its expression is strongly associated with patient outcome,clinical features,immune infiltration,tumour microenvironment,microsatellite instability,immune neoantigen,DNA mismatch repair and methyltransferase in a wide range of tumour patients.2.The verification results of gene expression data of ESCA GSE100942 chip in GEO database showed that PCAT6 was highly expressed in ESCA.Kaplan-Meier database analysis showed that high PCAT6 expression was associated with low survival rate in ESCA patients.Involvement of the JAK/STAT pathway in the functionalmechanism of PCAT6 revealed by GSEA enrichment analysis.3.The proliferation,invasion,and migration capacity of ESCC cells and the decrease in the expression of tumour stem cell-related genes(SOX2,SOX9,OCT4,and NANOG)are associated with the knockdown of PCAT6 expression in ESCC EC109 cells.4.Knockdown of PCAT6 in ESCC EC109 cells inhibited the mRNA expression levels of JAK2 and CCND1 genes and inhibited the protein expression levels of JAK2,pJAK2,p-STAT3,and CCND1.Conclusion: The expression of PCAT6 varies significantly in different tumour tissues and is closely related to patient prognosis.Of these,PCAT6 is highly expressed in ESCC and associated with poor prognosis.This study shows that PCAT6 promotes the progression and stemness of ESCC by activating the JAK/STAT signalling pathway.This study elucidated the effect of PCAT6 on ESCC progression,clarified the regulation of PCAT6 on the JAK/STAT pathway,and revealed a novel regulatory mechanism involved in ESCC development.