The effect of LOXL2 in hepatocellular carcinoma

Abstract

Lysyl oxidase-like 2 (LOXL2) is key in the hepatocellular carcinoma (HCC) tumor microenvironment and metastatic niche formation. However, its effect on proliferation and clinical parameters in HCC require further elucidation. The present study aimed to investigate LOXL2 expression in HCC from in vitro and clinical aspects. The present study constructed LOXL2-small interfering RNA with a lentiviral vector, investigated the effect of LOXL2 on proliferation using HCC cell lines via a series of assays, including reverse transcription-quantitative polymerase chain reaction, cell counting, colony formation, assessment of cell cycle and apoptosis using flow cytometry, MTT and BrdU. Furthermore, 80 tissue samples from HCC patients at The First Affiliated Hospital of Dalian Medical University (Dalian, China) from 2007 to 2010. Immunohistochemical staining was used to clinically verify LOXL2 expression. The results of the present study demonstrate that LOXL2 silencing decreased cell numbers, proliferation, colony formations and cell growth, induced cell cycle arrest and increased apoptosis. Clinically, expression levels of LOXL2 was markedly increased in matched adjacent non-tumor tissue (ANT) samples compared with levels in tumor tissue (TT) samples, and this gradually increased with higher histological grade and more advanced TNM classification in the matched ANT and TT samples. LOXL2 was determined to promote proliferation of HCC and demonstrated to be highly expressed in HCC ANT samples compared with TT samples.

Exosome-mediated secretion of LOXL4 promotes hepatocellular carcinoma cell invasion and metastasis

“…Other researchers and we have demonstrated that the expression of LOXL4 is upregulated in several human cancers, including head and neck squamous cell carcinoma (HNSCC) [47], laryngeal squamous cell carcinoma [49], and gastric cancer [11]. Others have shown that LOXL2 is frequently overexpressed in human HCC [50, 51], and we showed that LOXL4 expression was also increased at both mRNA and protein levels in HCC. Furthermore, we found that LOXL4 upregulation was significantly correlated with tumor differentiation, vascular invasion, and TNM stage and predicted a poor prognosis, in contrast to a previous study demonstrating that LOXL4 is downregulated in HCC tissues, and the downregulation is correlated with aggressive tumors and a worse clinical outcome [12].…”

Significance of Lysyl oxidase‑like�2 gene expression on the epithelial‑mesenchymal status of hepatocellular carcinoma

“…Several limitations of the present study should be acknowledged. Firstly, the study was retrospectively designed, although the results were in accordance with previous studies (28,38). Secondly, we only assessed the mRNA expression.…”

LOXL2 upregulates hypoxia‑inducible factor‑1α signaling through Snail‑FBP1 axis in hepatocellular carcinoma cells

“…It is involved in the progression of tumor progression and metastasis (31,49,(51)(52)(53). Upregulated expression of LOXL2 has been revealed in several types of cancer, including HCC (54). Extracellularly, LOXL2 can catalyze the covalent cross-linkages of collagen and elastin in the extracellular matrix.…”

“…There have been numerous studies that have revealed the expression of LOXL2, Snail and FBP1 in human HCC tissues. For example, LOXL2 was revealed to be frequently overexpressed in human HCC and displayed poor prognosis (54,(58)(59)(60). High expression of Snail or decreased expression of FBP1 was correlated with poor outcomes in HCC patients (61)(62)(63)(64)(65)(66).…”