Lamp2 inhibits epithelial-mesenchymal transition by suppressing Snail expression in HCC

Abstract

Lysosomal associated membrane protein 2 (Lamp2) influences a broad range of physiological and pathological processes. However, little is known about the role of Lamp2 in hepatocellular carcinoma (HCC) metastasis. This study found that Lamp2 expression was significantly lower in HCC tissues than in adjacent nontumor tissues (ANTs), and its expression level correlated with HCC metastasis. Low Lamp2 expression was significantly correlated with the AFP serum level (> 20 ng/Ml, P = 0.024), capsular formation (absent, P = 0.024), and microvascular invasion (present, P < 0.001), and low expression of Lamp2 indicated a poor prognosis in HCC. LowLamp2 expression was an independent and significant risk factor for recurrence-free survival (RFS; P < 0.001) and overall survival (OS; P < 0.001) in HCC. In this study, we demonstrated that Lamp2 overexpression inhibited cell motility and invasiveness in vitro and inhibited lung metastasis in vivo. In addition, Lamp2 could reverse the EMT program. Lamp2 silencing by siRNA in HCC cell lines enhanced the expression of mesenchymal markers and decreased the expression of epithelial markers. Consistent with these findings, Lamp2 overexpression had the opposite effects. Mechanistically, we found that Lamp2 could suppress Snail expression, upregulate E-cadherin, and inhibit HCC cell epithelial-mesenchymal transition (EMT).Together, these findings suggest that Lamp2 attenuates EMT by suppressing Snail expression in HCC.

Identifying an Eight-Gene Signature to Optimize Overall Survival Prediction of Esophageal Adenocarcinoma Using Bioinformatics Analysis of ceRNA Network

“…35 The roles of LAMP2 in EMT were demonstrated. 37 The above three genes were not only involved in the pathogenesis of cancer, but also found in our study to be significant DEmRNAs, suggesting that these genes may play an important role in the development and progression of EAC. Based on the above results, we carried out GO enrichment analysis of these eight genes.…”

Hepatitis B surface antigen expression impairs endoplasmic reticulum stress-related autophagic flux by decreasing LAMP2

“…A previous study also showed that HCC tissues expressed significantly less LAMP2 than adjacent tissues, and its expression level correlated with HCC metastasis. 35 Their results are consistent with ours, but they did not explain the reason for the decrease in LAMP2, which is thought to be influenced by HBsAg expression. In this study, HBsAg-induced ATF4 and ATF6 were identified as negative transcriptional regulators of LAMP2.…”

Clinical Significance of Apurinic/Apyrimidinic Endodeoxyribonuclease 1 and MicroRNA Axis in Hepatocellular Carcinoma

“… 46 However, contrasting information about LAMP2 expression and its role in HCC exists. Indeed, low LAMP2 expression seems to be correlated with microvascular invasion and poor prognosis in HCC, 47 while other studies demonstrated that increased stability of the protein mediated by the long noncoding RNA FAM215A, induces doxorubicin resistance and tumor progression. 39 Altogether this evidence suggests that APE1 may sustain HCC tumor progression through miRNAs regulation.…”