FXR1 promotes proliferation, invasion and migration of hepatocellular carcinoma in vitro and in vivo

Abstract

Hepatocellular carcinoma (HCC) is a common malignancy that is associated with a poor prognosis. The extensively studied TGF-β pathway is mediated by SMAD proteins. FXR1, a protein-coding gene belonging to the fragile X-related (FXR) family, is involved in the TGF-β pathway. Previous studies have shown that FXR1 promotes the proliferation, invasion, and migration of colorectal cancer cells. The aim of the present study was to explore the effects of FXR1 on HCC via the TGF-β/SMAD signaling pathway. Immunohistochemical analysis was used to detect the expression of FXR1 in HCC and normal tissues. Western blotting was used to detect protein expression levels in the HCC cell lines, cell migration and invasion were assessed using Transwell assays, and cell proliferation was assessed using a colony formation assay. The ability of the liver cancer cells to grow in vivo was investigated using a nude mouse tumor-bearing model. The results showed that FXR1 expression was upregulated in HCC tissues compared with normal tissues. Knockdown of FXR1 resulted in reduced expression of SMAD2/3 and EMT-related proteins in HCC cells. In addition, FXR1 knockdown inhibited the proliferation, migration, and invasion of HCC cells. FXR1 knockdown also reversed the promoting effect of TGF-β on the invasive ability of HCC cells. Knockdown of SMAD2/3 reversed the increase in HCC cell invasion induced by FXR1 overexpression. Finally, upregulated FXR1 expression was associated with a poorer prognosis in patients with HCC. In conclusion, FXR1 promoted HCC proliferation, migration, and invasion through the regulation of SMAD2/3.

The integration of machine learning and multi-omics analysis provides a powerful approach to screen aging-related genes and predict prognosis and immunotherapy efficacy in hepatocellular carcinoma

“…NDRG1 can enhance the interaction between fibroblasts and tumor cells, leading to the development of hepatocellular carcinoma [30,31]. FXR1 can promote the proliferation, invasion, and migration of hepatocellular carcinoma, and its action is mediated by Smad2/3 [32]. These studies provide additional evidence for the reliability of the genes we screened and are consistent with our predicted results.…”

Comprehensive bioinformatics analysis of FXR1 across pan-cancer: Unraveling its diagnostic, prognostic, and immunological significance

“…Our verification of FXR1 overexpression in numerous types of tumors, with some results corroborated by previous studies, supports this perspective. [6,[14][15][16] The prognostic implications and potential impact on tumorigenic processes of FXR1 expression levels in various human cancers remain unexplored and necessitate additional research. To our knowledge, this study represents the inaugural comprehensive examination of FXR1's expression and biological functionality from a pan-cancer viewpoint.…”

“…[55] In the context of hepatocellular carcinoma, FXR1 has been established as a factor that stimulates cell growth, movement, and infiltration by influencing the participation of SMAD2/3 in the TGF-β pathway. [15] Additionally, FXR1 expression has been directly linked to the survival and proliferation of cancer cells, as it facilitates the cyclization of cMYC mRNA and promotes the recruitment of eukaryotic translation initiation factors to translation initiation sites, thereby elevating cMYC levels in cancer cells. [4] Nowadays, an increasing number of studies have demonstrated the critical role of the immune microenvironment in the development and progression of tumors.…”