LINC01225 Promotes Occurrence And Metastasis Of Hepatocellular Carcinoma In An Epidermal Growth Factor Receptor-dependent Pathway

Objective:Long noncoding RNAs (lncRNA) have been confirmed as biomarkers in hepatocellular carcinoma (HCC). We aimed to identify an HCC-related lncRNA and elucidate its functional roles in the development and progression of HCC.Methods:The expression level of LINC01225 mRNA was detected in HCC tissues, serum and cell lines by quantitative real time PCR. LINC01225 stably knockdown cells were developed with short hairpin RNAs (shRNAs). Over-expression of LINC01225 in LINC01225 knockdown cells was also performed. The effect of LINC01225 on cell proliferation and invasion was studied in vitro. Cell apoptosis and cell cycle was detected by flow cytometry analysis (FCA). Mice model was used to explore the roles of LINC01225 in tumor progression and metastasis in vivo. Regulatory mechanism of LINC01225 in HCC was studied by microarray, Mass spectrometry, RNA immunoprecipitation. Finally, analysis was performed to identify the function in the prediction of diagnosis and prognosis.Resμlts:We showed that LINC01225 was upregulated in HCC. Knockdown of LINC01225 inhibited cell proliferation and invasion via activated apoptosis and cell cycle arrest in vitro. Over-expression of LINC01225 in LINC01225 knockdown cells presented that attenuated cell proliferation and invasion was restored and enhanced. Subcutaneous and tail vein/intraperitoneal injection xenotransplantation model in vivo validated reduced tumor progression and metastasis. We found that LINC01225 could bind to epidermal growth factor receptor (EGFR) and increase the protein level of EGFR, subsequently fine tune the EGFR/Ras/Raf-1/MEK/MAPK signaling pathway. We also proved that high expression of LINC01225 was positively associated with poor prognosis and LINC01225 was stably and high expressed in HCC serum.Conclusion:LINC01225 plays a crucial role in HCC and can act as a biomarker for the diagnosis and prognosis of HCC.