The role of LASS2 in regulating bladder cancer cell tumorigenicity in a nude mouse model

Abstract

Previous in vitro studies have demonstrated that LAG1 longevity assurance homolog 2 (LASS2) is a novel tumor suppressor gene that is significantly associated with the proliferation and invasion ability of tumor cells. However, the role LASS2 serves in regulating bladder cancer cell tumorigenicity and tumor growth in vivo has not yet been elucidated in animal or clinical studies. In the present study, LASS2 knockdown in human bladder cancer EJ-M3 cells significantly promoted the growth of xenografts in nude mice compared with the control group, while overexpression of LASS2 suppressed tumor growth; however, this was not statistically significant. Furthermore, LASS2 knockdown resulted in more apparent heteromorphism and a higher activity of matrix metalloproteinase (MMP)-2 and MMP-9 in xenograft tumors. The data from the present study demonstrated that LASS2 knockdown significantly promoted the tumorigenicity and growth of EJ-M3 xenograft tumors in nude mice, and that LASS2 overexpression has a tendency to inhibit the growth of xenografts, suggesting that it may be a potential therapeutic target for bladder cancer.

The Role of Longevity Assurance Homolog 2/Ceramide Synthase 2 in Bladder Cancer

“…This correlation has also been tested experimentally, using nude mice to study the evolution of xenografts with a highly invasive human BC cell line. Indeed, when CERS2 was silenced in the xenografts, the resulting tumors significantly increased in volume [60]. Also supporting the tumor suppressor activity of CERS2, an epidemiology study based on SNPs showed that a particular substitution, which favors RNA instability and reduces transcript abundance, acts as an independent risk factor of BC susceptibility and clinical prognosis in the Chinese population [24].…”

Alternative splicing of ceramide synthase 2 alters levels of specific ceramides and modulates cancer cell proliferation and migration in Luminal B breast cancer subtype

“…C16:0 ceramides have been shown to play a pivotal role in cell migration during epithelial to mesenchymal transition in different cancer cell lines 59 . In contrast, overexpression of CERS2, that synthesizes very-long-chain ceramides, has been demonstrated to inhibit cancer cell proliferation and migration in prostate, breast, and bladder cancers 60 , 61 . Luminal B-specific BT-474 cells overexpressing PC transcript of CERS2 showed a significant decrease in cell proliferation and migration due to an increase in levels of very-long-chain ceramides.…”

Overexpression of close homolog of L1 enhances the chemosensitivity of lung cancer cells via inhibition of the Akt pathway

“…20190325) and were performed in compliance with all regulatory institutional guidelines for animal welfare (the National Institutes of Health Publications no. 80-23) ( 23 ). A total of 12 male BALB/c-nu mice (4-week-old, 20±5 g; Hunan SJA Laboratory Animals Center of the Chinese Academy of Sciences) were used in this study.…”