Study On The Molecule Mechanism Of WISP1 Overexpression Promote The Proliferation And Metastasis Of Esophageal Squamous Cellcarcinoma

Purpose Esophageal squamous cell carcinoma(ESCC)is one of the most common and aggressive human solid tumors with high mortality.However,the underlying mechanisms and influencing factors involved in ESCC progression remain unclear.Wnt1 inducible signaling pathway protein 1(WISP1)was reported to be a critical regulator of cancer development and progression.The aim of the present study was to explore the role of WISP1 in regulating the progression of ESCC.Method Differential expression profiles of m RNAs in ESCC were screened by microarray assay.The m RNA expression levels of WISP1 were detected by reverse transcription polymerase chain reaction(RT-PCR)in 78 ESCC patients.Immunohistochemistry(IHC)was performed to measure the protein expression levels of WISP1 in 43 ESCC patients.The relationship between WISP1 expression and clinical pathology of ESCC was analyzed.Changes in cell proliferation,invasion and metastasis were detected by silencing WISP1 in Eca109 and KYSE450 cells.Using RNA immunoprecipitation plus sequencing(RIP-Seq),lnc RNA binding to WISP1 protein was screened.Finally,lnc RNA HOTAIRM1(HOTAIRM1)was either knocked down or overexpressed in KYSE450 cells to observe changes in WISP1 protein expression using Western blotting assay,and cell proliferation,invasion and metastasis were detected using the MTT assay,cell invasion and Transwell assay.Result The results of gene chip,IHC and RT-PCR showed that WISP1 was highly expressed in ESCC,and lymph node metastasis was more common in ESCC patients with high expression of WISP1(P < 0.05).After silencing WISP1 in Eca109 and KYSE450 cells,cell proliferation was weakened,and the cell invasion and metastasis abilities were decreased.RIP-Seq method found that WISP1 protein could interact with lnc RNA HOTAIRM1.Knockdown or overexpression of HOTAIRM1 in KYSE450 cells either promoted or inhibited cell proliferation,invasion and metastasis,and increased or decreased the protein level of WISP1 respectively.Conclusion High expression of WISP1 suggested a higher rate of lymph node metastasis in ESCC.WISP1 expression was positively correlated with ESCC cell proliferation,invasion and metastasis.In contrast,HOTAIRM1 expression was negatively correlated with ESCC cell proliferation,invasion and metastasis by regulating WISP1 protein level in ESCC cells,suggesting that HOTAIRM1 may be a potential target to inhibit the WISP1 activity.