TROVE2 regulated invasion and migration of hepatocellular carcinoma cells via heparanase

Background:The role of TROVE domain family member 2(TROVE2)has been well-demonstrated in autoimmune diseases;however,its involvement in liver cancer remains unclear.Therefore,this study aimed to explore the biological function and clinical significance of TROVE2 in hepatocellular carcinoma(HCC).Methods:The expression level of TROVE2 was analyzed in HCC and paired adjacent tissue samples using real-time reverse transcription-quantitative polymerase chain reaction.The impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western blotting.High-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target genes.Back-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC cells.Results:TROVE2 exhibited significant overexpression in liver cancer tissue,correlating with shorter overall survival.Overexpression of TROVE2 facilitated the invasion,metastasis,and epithelial-mesenchymal transition(EMT)process of HCC cells,whereas TROVE2 knockdown restrained migration,invasion,and EMT in these cells.Transcriptome sequencing and bioinformatics analysis identified heparanase(HPSE)as a downstreamtarget protein of TROVE2.Subsequent back-complementation experiments provided evidence that HPSE overexpression promoted TROVE2-mediated prometastasis effects.Moreover,the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3βphosphorylation.Conclusions:TROVE2 facilitated the invasion,migration,and EMT process ofHCC cells through phosphorylation of the HPSE/GSK-3βaxis,indicating its significance as an important protein in tumor progression.

HIF-1αand HDAC1 mediated regulation of FAM99AmiR92a signaling contributes to hypoxia induced HCC metastasis

Dear Editor,Hypoxic microenvironment is clinically associated with metastasis and poor prognosis of numerous cancers.Previous studies have shown that many protein-coding genes and microRNAs are regulated upon hypoxia and involved in the progression of cancer.However,the roles of lncRNAs in the hypoxia-responsive gene networks and how lncRNA-related signaling network regulates hypoxia induced tumor metastasis is still not clear.

Quantitative Secretome Analysis Reveals Clinical Values of Carbonic Anhydrase Ⅱ in Hepatocellular Carcinoma

Early detection and intervention are key strategies to reduce mortality,increase longterm survival,and improve the therapeutic effects of hepatocellular carcinoma(HCC)patients.Herein,the isobaric tag for relative and absolute quantitation(iTRAQ)-based quantitative proteomic strategy was used to study the secretomes in conditioned media from HCC cancerous tissues,surrounding noncancerous tissues,and distal noncancerous tissues to identify diagnostic and prognostic biomarkers for HCC.In total,22 and 49 dysregulated secretory proteins were identified in the cancerous and surrounding noncancerous tissues,respectively,compared with the distal noncancerous tissues.Among these proteins,carbonic anhydrase II(CA2)was identified to be significantly upregulated in the secretome of cancerous tissues;correspondingly,the serum concentrations of CA2 were remarkably increased in HCC patients compared with that in normal populations.Interestingly,a significant increase of serum CA2 in recurrent HCC patients after radical resection was also confirmed compared with HCC patients without recurrence,and the serum level of CA2 could act as an independent prognostic factor for time to recurrence and overall survival.Regarding the mechanism,the secreted CA2 enhances the migration and invasion of HCC cells by activating the epithelial mesenchymal transition pathway.Taken together,this study identified a novel biomarker for HCC diagnosis and prognosis,and provided a valuable resource of HCC secretome for investigating serological biomarkers.