FLVCR1 promotes the proliferation and tumorigenicity of synovial sarcoma through inhibiting apoptosis and autophagy

Abstract

Feline leukemia virus subgroup C receptor 1 (FLVCR1) has been reported to have a crucial role in variety of biological processes, including cell proliferation, cell death, apoptosis, oxidative stress response, cellular differentiation and metabolism. However, little is known about its role in synovial sarcoma (SS). In the current study, FLVCR1 expression was analyzed in two SS cell lines (SW982 and HS-SY-II), and in eight SS tissues and paired adjacent non-tumor tissues using reverse transcription-quantitative polymerase chain reaction, western blot analysis and immunohistochemistry. Lentivirus-mediated short hairpin RNAs were used to knock down FLVCR1 expression in SW982 and HS-SY-II cells. The effects of FLVCR1 knockdown on the cell proliferation, clonogenicity, cell cycle and apoptosis in SS cells were evaluated by MTT, colony formation assay, flow cytometry analysis, western blotting and in vivo tumorigenesis in nude mice. In the current study, gene expression of FLVCR1 was upregulated in SS cell lines (SW982 and HS-SY-II) and SS tissues from patients. The protein levels of FLVCR1 in SS tissues were also significantly higher than in adjacent non-tumor tissues. Furthermore, suppressing the expression of FLVCR1 in SS cells using short hairpin RNA effectively attenuated cell proliferation, colony formation and impaired the cell cycle, and also significantly induced apoptosis and autophagy. In accordance with this, an in vivo tumorigenicity assay in mice demonstrated that suppression of FLVCR1 expression inhibited the growth of SS tumors implanted subcutaneously. Collectively, these results demonstrated that FLVCR1 may act as an oncoprotein, and have key roles in promoting proliferation and tumorigenicity of SS, and this may shed new light on finding novel therapeutic strategies against SS.

FLVCR1 Predicts Poor Prognosis and Promotes Malignant Phenotype in Esophageal Squamous Cell Carcinoma via Upregulating CSE1L

“…Recent studies have focused on the crucial role of FLVCR1 in tumor promotion. For instance, upregulated FLVCR1 promoted the cellular proliferation of neuroblastoma and synovial sarcoma ( 9 , 10 ). Aberrant expression of FLVCR1 was correlated with aggressive tumor stage and poor survival in hepatocellular carcinoma ( 11 ).…”

Identification of Iron Metabolism-Related Genes Signature and Novel Role of FLVCR1 in Hepatocellular Carcinoma

“…In addition, the carcinogenesis of FLVCR1 in several malignancies has gradually been uncovered. For example, Changliang Peng found FLVCR1 can promote the proliferation of synovial sarcoma through regulating autophagy (32). Although, Xianli Wei, reported the expression of FLVCR1 in HCC tumor tissues was upregulated compared with the adjacent non-tumor tissues (33), the role of FLVCR1 in progression of HCC is still unclear.…”

Identification and Validation of a Novel Metabolism‑Related Prognostic Signature in Hepatocellular Carcinoma

“…In addition, little is known about the roles of COX7B2 in human cancers and other diseases. Feline leukemia virus subgroup C receptor 1(FLVCR1) encoding a ubiquitous heme exporter was demonstrated to promote the proliferation and tumorigenicity through inhibiting apoptosis and autophagy [35,36].…”