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 ... -  《-》

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 ... -  《-》

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain-dependent regulation of Wnt/β-catenin signaling.

Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss-of-function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/β-catenin signaling as well as its target genes, c-Myc and cyclin D1. Interesting, the tumor-suppressive function of SOX6 was proved to be dependent on its specific high-mobility-group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/β-catenin signaling pathway in an HMG domain-dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.

Chen L ，Xie Y ，Ma X ，Zhang Y ，Li X ，Zhang F ，Gao Y ，Fan Y ，Gu L ，Wang L ，Zhang X ，Fu B ... -  《-》

Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/β-catenin signaling pathway.

Wang G ，Zhang ZJ ，Jian WG ，Liu PH ，Xue W ，Wang TD ，Meng YY ，Yuan C ，Li HM ，Yu YP ，Liu ZX ，Wu Q ，Zhang DM ，Zhang C ... -  《Molecular Cancer》

Long non-coding RNA CCAT2 promotes cell proliferation and invasion through regulating Wnt/β-catenin signaling pathway in clear cell renal cell carcinoma.

Huang JL ，Liao Y ，Qiu MX ，Li J ，An Y ... -  《-》