Downregulation of UBAP2L Inhibits the Epithelial-Mesenchymal Transition via SNAIL1 Regulation in Hepatocellular Carcinoma Cells.
OBJECTIVE
Dysregulation of ubiquitin-associated protein 2-like (UBAP2L) has been reported in tumors, but its role in hepatocellular carcinoma (HCC) progression is unclear.


METHODS
The expression levels of UBAP2L in HCC tissues and HCC cell lines were detected by western blot and quantitative real-time (qRT) PCR. The effects of UBAP2L expression on HCC cell biological traits, including migration and invasion, were investigated by wound healing assay and matrigel transwell assay. Simultaneously, the expression of epithelial-mesenchymal transition (EMT) markers including E-cadherin, CK-18, N-cadherin, Vimentin, Claudin7 and the promoter activity of E-cadherin were detected by western blot and qRT-PCR. Subsequently, role of SNAIL1 in UBAP2L-mediated EMT and the mechanism underlying UBAP2L-mediated SNAIL1 expression were further investigated.


RESULTS
UBAP2L was overexpressed in human HCC tissues compared with peri-tumoral tissues. Downregulation of UBAP2L inhibited migration, invasion and the EMT in highly metastatic HCC cell lines. Furthermore, UBAP2L knockdown inhibited expression of the transcriptional repressor SNAIL1 and its ability to bind to the E-cadherin promoter via SMAD2 signaling pathway, which in turn resulted in increased E-cadherin expression. Additionally, bioinformatics analysis showed that expression of UBAP2L is correlated with poor prognosis in patients with HCC.


CONCLUSIONS
UBAP2L plays a critical role in maintenance of the metastatic ability of HCC cells via SNAIL1 Regulation and is predictive of a poor clinical outcome.
Minhang hospital, Fudan University, Shanghai, China.
Tao
T
Ye
Minhang hospital, Fudan University, Shanghai, China.
Jing
J
Xu
Minhang hospital, Fudan University, Shanghai, China.
Ling
L
Du
Minhang hospital, Fudan University, Shanghai, China.
Wenhui
W
Mo
Shanghai Cancer Center, Fudan University, Shanghai, China.
Yiming
Y
Liang
Minhang hospital, Fudan University, Shanghai, China.|Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.
Jinglin
J
Xia
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D015996:Survival Rate
D002352:Carrier Proteins; D009363:Neoplasm Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C000595671:Ubap2L protein, human
E-cadherin; Epithelial-mesenchymal transition; Hepatocellular carcinoma; SNAIL1; Ubiquitin associated protein 2-like