NLRC5 regulates cell proliferation, migration and invasion in hepatocellular carcinoma by targeting the Wnt/β-catenin signaling pathway.

NLRC5, the largest member of nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family, has been reported to regulate immune responses and is associated with chronic inflammatory diseases. However, the biological function of NLRC5 in hepatocellular carcinoma (HCC) has not yet been well demonstrated. In this study, the role of NLRC5 in hepatocellular carcinoma cell proliferation, migration and invasion capacities was evaluated by using MTT, flow cytometry, wound healing, transwell assay, and tumor formation assay in nude mice. Western blot analysis and qPCR assay were performed to assess NLRC5 interacting with the activation of Wnt/β-catenin signaling pathway. Here, we demonstrate that NLRC5 was highly expressed in HCC. Knockdown of NLRC5 significantly inhibited cell proliferation, migration, invasion and the tumor formation in nude mice, and arrested the cell cycle at G0/G1 phase. Furthermore, overexpression of NLRC5 promoted the proliferation, migration and invasion of HCC cells in vitro. Interestingly, we found that up-regulation of NLRC5 not only positively correlates with the increase of β-catenin but also coordinates the activation of downstream Wnt/β-catenin signaling pathway. Thus, our findings suggest that NLRC5 may play an important role in progression of HCC and provide a potential therapeutic value in this tumor.

Peng YY ，He YH ，Chen C ，Xu T ，Li L ，Ni MM ，Meng XM ，Huang C ，Li J ... -  《-》

Metallothionein 1H (MT1H) functions as a tumor suppressor in hepatocellular carcinoma through regulating Wnt/β-catenin signaling pathway.

Zheng Y ，Jiang L ，Hu Y ，Xiao C ，Xu N ，Zhou J ，Zhou X ... -  《BMC CANCER》

NLRC5 mediates cell proliferation, migration, and invasion by regulating the Wnt/β-catenin signalling pathway in clear cell renal cell carcinoma.

NLRC5, a newly discovered member of the NLR family, has been reported to regulate immune responses and promote cell proliferation, migration, and invasion in hepatocellular carcinoma. However, to date, the potential regulatory roles and molecular mechanisms by which NLRC5 affects the development and progression of clear cell renal cell carcinoma (ccRCC) remain largely unknown. In this study, human clinical data from The Cancer Genome Atlas database revealed that increased NLRC5 expression was associated with advanced stage and poor prognosis in ccRCC patients. Moreover, experimental results showed that NLRC5 is aberrantly overexpressed in human ccRCC tissues and cell lines. Depletion of NLRC5 attenuated ccRCC cell proliferation, migration, and invasion and suppressed ccRCC growth in a nude mouse model. By contrast, overexpression of NLRC5 promoted the proliferation, migration, and invasion of ccRCC cells in vitro. Additionally, NLRC5 expression is not only positively correlated with β-catenin but also coordinates the activation of the downstream Wnt/β-catenin signalling pathway. Together, our data suggest that NLRC5 may be a potential therapeutic target for ccRCC therapy.

Wang Q ，Ding H ，He Y ，Li X ，Cheng Y ，Xu Q ，Yang Y ，Liao G ，Meng X ，Huang C ，Li J ... -  《-》

UNC119 promotes the growth and migration of hepatocellular carcinoma via Wnt/β/catenin and TGF/β-EMT signaling pathways.

Liu Z ，Zhang Y ，Xu Z 《Journal of BUON》

CUL4B activates Wnt/β-catenin signalling in hepatocellular carcinoma by repressing Wnt antagonists.

Activation of Wnt/β-catenin signalling is frequently observed in many types of cancer including hepatocellular carcinoma (HCC). We recently reported that cullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, is overexpressed in many types of solid tumours and contributes to epigenetic silencing of tumour suppressors. In this study, we characterized the function of CUL4B in HCC and investigated whether CUL4B is involved in the regulation of Wnt/β-catenin signalling. CUL4B and β-catenin were frequently up-regulated and positively correlated in HCC tissues. CUL4B activated Wnt/β-catenin signalling by protecting β-catenin from GSK3-mediated degradation, achieved through CUL4B-mediated epigenetic silencing of Wnt pathway antagonists. Knockdown of CUL4B resulted in the up-regulation of Wnt signal antagonists such as DKK1 and PPP2R2B. Simultaneous knockdown of PPP2R2B partially reversed the down-regulation of β-catenin signalling caused by CUL4B depletion. Furthermore, CRL4B promoted the recruitment and/or retention of PRC2 at the promoters of Wnt antagonists and CUL4B knockdown decreased the retention of PRC2 components as well as H3K27me3. Knockdown of CUL4B reduced the proliferation, colony formation, and invasiveness of HCC cells in vitro and inhibited tumour growth in vivo, and these effects were attenuated by introduction of exogenous β-catenin or simultaneous knockdown of PPP2R2B. Conversely, ectopic expression of CUL4B enhanced the proliferation and invasiveness of HCC cells. We conclude that CUL4B can up-regulate Wnt/β-catenin signalling in human HCC through transcriptionally repressing Wnt antagonists and thus contributes to the malignancy of HCC.

Yuan J ，Han B ，Hu H ，Qian Y ，Liu Z ，Wei Z ，Liang X ，Jiang B ，Shao C ，Gong Y ... -  《-》