CARMA3/NF-κB signaling contributes to tumorigenesis of hepatocellular carcinoma and is inhibited by sodium aescinate

Abstract

BACKGROUNDPrimary hepatocellular carcinoma (HCC) is a very malignant tumor in the world. CARMA3 plays an oncogenic role in the pathogenesis of various tumors. However, the function of CARMA3 in HCC has not been fully clarified.AIMTo study the biological function of CAEMA3 in HCC.METHODSTissue microarray slides including tissues form 100 HCC patients were applied to access the expression of CARMA3 in HCC and its clinical relevance. Knockdown and overexpression of CARMA3 were conducted with plasmid transfection. MTT, colony formation, and apoptosis assays were performed to check the biological activity of cells.RESULTSHigher expression of CARMA3 in HCC was relevant to poor prognostic survival (P < 0.05). Down-regulation of CARMA3 inhibited proliferation and colony formation and induced apoptosis in HCC cell lines, while increasing its expression promoted tumorigenesis. We also found that sodium aescinate (SA), a natural herb extract, exerted anti-proliferation effects in HCC cells by suppressing the CARMA3/nuclear factor kappa-B (NF-κB) pathway.CONCLUSIONOverexpression of CARMA3 in HCC tissues correlates with a poor prognosis in HCC patients. CARMA3 acts pro-tumorigenic effects partly through activation of CARMA3/NF-κB. SA inhibits HCC growth by targeting CARMA3/NF-κB.

CARMA3: A potential therapeutic target in non-cancer diseases

“…Moreover, CARMA3 promotes cell invasion and migration, and is positively correlated with lung cancer stemness, metastasis, and poor survival outcomes ( 54 ). Similar results have been observed in hepatocellular carcinoma ( 56 ), colorectal cancer ( 57 , 58 ), ovarian cancer ( 59 ), breast cancer ( 60 , 61 ), and renal cell carcinoma ( 62 – 64 ). In conclusion, CARMA3 is involved in the development and pathogenesis of various types of cancers.…”

CARMA3 Promotes Colorectal Cancer Cell Motility and Cancer Stemness via YAP-Mediated NF-κB Activation

“…CARMA3 has been shown to be overexpressed in various human cancers [ 3 ]. Several studies reported that inhibition of CARMA3 decreased cell proliferation, migration, and tumor growth in NSCLC, bladder cancer, hepatocellular carcinoma, renal cell carcinoma, and colorectal cancer [ 4 , 5 , 6 , 7 , 8 ]. CARAM3 enhanced nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation by regulating the downstream IKK complex activity in response to RTKs and PKC stimulation [ 9 , 10 ].…”

Solid lipid nanoparticles as an effective sodium aescinate delivery system: formulation and anti-inflammatory activity

“…Therefore, particle size was rst analyzed by Design Expert 8.0.7 soware. The tting equation was described as following: PS ¼ 134.38 + 46.63A À 32.30B À 6.88C À 38.35AB + 12.26AC + 1.65BC + 26.68A 2 À 1.61B 2 + 11.18C 2 The results implied that the quadratic model was signicant. The P values of A, B, AB, and A 2 were all less than 0.05, suggesting that they had a considerable inuence on the PS of SLNs.…”

“…Sodium aescinate (SA) is a triterpene saponin extracted from the dried fruits of Aesculus wilsonii Rehd . A number of studies have shown the therapeutic properties of SA, such as anti-inflammation, 1 anti-exudation, 2 detumescence, 3 and antioxidant effects; 4 it also can increase venous tension 5 and improve blood circulation. 6 …”