Table 1.

Studies ascribing antitumor or protumor roles to NLRC5.

Cancer Type	Model Systems	Study Description	Molecular Effects	Ref.
NLRC5 as a tumor suppressor
Melanoma	Murine B16.F10 cell line stably expressing NLRC5	NLRC5 limits tumor growth and metastasis in C57BL/6 mice by activating antitumor CD8+ T lymphocytes;	NLRC5 upregulates MHC-I, β2M, PSMB9, PSMB8, TAP1 gene expression; NLRC5 promotes presentation of peptide from gp100 (Pmel-1) tumor antigen	[208]
Melanoma	PRMT5 knockdown in B16.F10 and Yummer1.7 cell lines; B16.F10 stably expressing NLRC5	Induction of endogenous NLRC5 by PRMT5 knockdown, or stable NLRC5 expression inhibited tumor growth in C57BL/6 mice	PRMT5 reduces NLRC5 expression by promoting methylation of Arg residues on histones	[176]
Melanoma	Jak1−/−B16 cell line expressing NLRC5	NLRC5 rendered Jak1−/− B16 cells susceptible to killing by adoptively transferred Pmel-1 TCR transgenic CD8+ T cells in vivo	NLRC5 upregulates MHC-I	[210]
Pancreatic adeno-carcinoma (PDAC)	Murine Panc02 cell line expressing a model antigenic peptide SIYRYYGL fused to GFP (Panc02SIY100)	Gamma irradiation induces NLRC5 expression renders Panc02 cells susceptible to anti-PD-L1 in vivo; Stable NLRC5 expression in Panc02SIY100 promotes activation of 2C TCR transgenic CD8+ T lymphocytes	Gamma irradiation induces MHC-I independently of IFN-I signaling	[178]
NLRC5 as a tumor promoter
Hepatocellular carcinoma (HCC)	Human HCC specimens; HCC cell lines: HepG2, SMMC-7721, BEL-7402; stable expression or knockdown of NLRC5	HCC specimens and cell lines display elevated NLRC5 expression; NLRC5 promotes cell proliferation, migration and invasion; NLRC5 knockdown has opposite effect & reduces HepG2 tumor growth in nude mice	NLRC5 expression promotes Wnt/β-catenin signaling and c-Myc, CyclinD1, MMP3 expression; β-catenin inhibitor iCRT3 attenuated the effects of NLRC5 overexpression	[211]
Hepatocellular carcinoma	HepG2 cell line	NLRC5 overexpression in HepG2 cells promotes cell growth via upregulating VEGF-A	NLRC5 promotes VEGF-A expression via AKT activation	[213]
Clear cell renal cell carcinoma (ccRCC)	Human ccRCC specimens Human ccRCC cell lines Caki-1, 786-O and 769-P	ccRCC specimens and cell lines display elevated NLRC5 expression; NLRC5 promotes cell proliferation, migration and invasion; NLRC5 knockdown causes opposite effects and reduces 786-O tumor growth in nude mice	NLRC5 promotes β-catenin, c-Myc, CyclinD1, MMP2, MMP9 expression	[212]
Giloma	Human glioma tissues, cell lines U87, U251	High grade glioma tissues and cell lines display elevated NLRC5 expression due to high levels of lncRNA SCAMP1; NLRC5 knockdown restrains cell proliferation, migration & invasion and increases apoptosis	SCAM1-1 sponges off miR-499a-5p, which targets LMX1A; LM1A binds NLRC5 promoter and is proposed to augment NLRC5 expression to activate the Wnt/β-catenin pathway	[192]
Esophageal squamous cell carcinoma (ESCC)	ESCC cell lines	NLRC5 overexpression in ESCC cell lines promotes cell proliferation, colony formation and cell cycle progression	miR-4319 targets NLRC5; low miR-4319 in ESCC upregulates NLRC5 expression	[215]
Breast cancer	Breast cancer tissues, cell lines MCF-7, MDA-MB-231	MCF-7 and MDA-MB-231 show increased proliferation, migration and invasion due to elevated expression of XIST lncRNA, which upregulates NLRC5	XIST sponges off miR-125b-5p, which targets NLRC5	[197]