MALT1 expression

Our findings illustrated that ChREBP is an oncogene in the human prostate. High glucose condition induces a glucose/ChREBP/MALT1/NF-κB axis which links the glucose metabolism to the NF-κB activation in prostate cancer cells, and a glucose/ChREBP/WISP1 axis mediating autocrine and paracrine signaling between fibroblasts and cancer cells to promote cell migration, contraction, growth, and invasion of the human prostate.

Blood MALT1 measurement may assist in predicting outcomes in psoriasis patients, especially in those receiving biologics.

Overall, our data reveal a previously unrecognized role of the MALT1-LPCAT3 axis in osteoarthritis. Targeting the MALT1-LPCAT3 pathway with MALT1 inhibitors or siRNA-liposomes of LPCAT3 may become an effective strategy to treat OA by suppressing eicosanoids, matrix-degrading enzymes, and proinflammatory cytokines.

The effects of MALT1 and mechanistic target of rapamycin (mTOR) on T-cell immunity were investigated through western blot, CCK8 assay, and flow cytometry...MALT1 expression is aberrant in both local lesions and peripheral blood of OLP. Inhibition of the mTOR pathway further enhances the suppression of T-cell proliferation and the promotion of apoptosis induced by the MALT1 inhibitor MI-2.

Furthermore, LvMALT1 is prominently upregulated in response to a challenge by the white spot syndrome virus (WSSV), facilitating the NF-κB-mediated expression of AMPs as a defense against viral infection. Taken together, we identified a MALT1 homolog from the shrimp L. vannamei, which plays a positive role in the TRAF6/NF-κB/AMPs axis-mediated innate immunity.

Moreover, silencing of Tensin-3 expression in MALT1-driven lymphoma promoted dissemination of xenografted lymphoma cells to the bone marrow and spleen. Thus, MALT1-dependent Tensin-3 cleavage reveals a unique aspect of the function of MALT1, which negatively regulates integrin-dependent B cell adhesion and facilitates metastatic spread of B cell lymphomas.

Decreased MALT1 expression after treatment and a decline in MALT1 expression of >30% after treatment (ratio to MALT1 before treatment) (both P≤0.001) presented more significant associations with prolonged PFS and OS times. In conclusion, early low levels of blood MALT1 during therapy may predict an improved response to PD-1 inhibitor-based treatment and survival time in patients with mCRC.

Finally, we show that MALT1 expression is positively correlated with NF-kB activation in human HCC tissues and cell lines, suggesting that its tumor promoting functions may involve functional interaction with the NF-kB signaling pathway. This work unveils new insights into the molecular implications of MALT1 in hepatocarcinogenesis and places this paracaspase as a potential marker and druggable liability in HCC.

Ectopic ARv7 overexpression not only enhanced 22Rv1 or PC-3 cell growth and invasion in vitro but also the tumor growth of PC-3 cells in vivo. These results indicate that an androgen receptor induces MALT1 expression androgen-dependently and -independently in ARFL- or ARv7-overexpressed prostate cancer cells, suggesting a novel ARv7/MALT1/NF-κB-signaling pathway may exist in the cells of prostate cancer.

Furthermore, MALT1 knockdown suppressed NF-κB pathway activation validated by immunofluorescence staining and western blot assays (all P < 0.05). MALT1 knockdown improves functional recovery, attenuates microglia activation, M1 polarization, and neuroinflammation via inhibiting NF-κB pathway in SCI.

Blockage of MALT1 with its inhibitor or siRNA reduced STEP61 degradation, accompanied by a decrease in GluN2B phosphorylation, intracellular calcium concentration, and brain cell injury, which were reversed by overexpression of MALT1. Based on these observations, we conclude that the downregulation of HECTD4 in ischemic stroke rat brain accounts for calcium overload and brain injury due to activating GluN2B directly and indirectly through a mechanism involving the reduced ubiquitination of GluN2B and MALT1, respectively.

Furthermore, MALT1 increment during induction treatment < 50% was related to unsatisfied accumulating EFS (P = .001) and OS (P = .007). PBMC MALT1 deficiency is common and relates to unfavorable induction therapy response and survival profile in AML patients.

MALT1 was positively linked to 24 h proteinuria (r=0.473, P=0.008), Scr (r=0.378, P=0.039), and C-reactive protein (CRP) (r=0.410, P=0.025) in LN patients. MALT1 might serve as a useful biomarker for estimating the disease risk in LN patients; however, future large-sample size studies need to be conducted to validate our findings.

Over-expression of MALT1 attenuated neuroprotective effects of HECTD3 silencing on high glucose-induced PC12 cells. HECTD3 silencing exerted neuroprotective effect against DACD through MALT1-mediated JNK signalling.HighlightsHECTD3 was up-regulated in hippocampus of streptozotocin-induced diabetic rats and high glucose-induced PC12.Knockout of HECTD3 promoted in vivo neuronal survival, reduced inflammation and pyroptosis, and improved the learning and memory function in diabetic rats.Knockout of HECTD3 suppressed the activation of NLRP3 inflammasome in diabetic rats.Silencing of HECTD3 exerted neuroprotective effects through MALT1-mediated JNK signalling.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 positively correlates with Th17 cells, inflammatory, and activity degree; meanwhile, its decrement along with treatment reflects the response to TNF inhibitor in AS patients.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 serves as a potential biomarker for monitoring exacerbation risk and Th1/Th2 imbalance-mediated inflammation of asthma children.

PBMC MALT1 is highly expressed in sepsis patients with its overexpression associated with multiple organic dysfunctions, elevated Th17 cells, and increased mortality risk.

Moreover, in rats with an E. coli-induced UTI model, allicin significantly alleviated the infection and up-regulation of MALT1 expression in the bladders, a marked increase in the bacterial load of urine, and deviations in serum biochemical parameters. In conclusion, allicin exerts anti-infective effects in UTIs mainly via the MALT1/NF-κB axis or AKT/NF-κB pathway, which provides a theoretical basis for understanding the function of allicin against UTIs and facilitates its clinical application.

MALT1 serves as a potential biomarker for disease surveillance and treatment response prediction of IBD patients.

Mechanistically, miR-375 and miR-365a-3p were identified to inhibit NF-κB activation via targeting MALT1. Overall, our results highlight that a novel regulatory axis, miRNA-MALT1-NF-κB, plays a vital role in the progression of CRC and provides novel and hopeful therapeutic targets for clinical treatment.

Collectively, our study clarified the role of miR-3681-5p/MALT1 axis underlying the oncogenic function of lncRNA HOXD-AS2 in GBM. Future work is required to study the mechanism by which HOXD-AS2 is upregulated in GBM cells, which can provide novel insights into therapeutic intervention for GBM treatment.

CAPE induced the ERK/JNK/p38/AMPKα1/2 signaling pathways; however, pretreatment with the corresponding inhibitors of MAPK or AMPK1/2 did not inhibit the CAPE effect on MALT1 blocking in PC-3 cells. Our findings verify that CAPE is an effective antitumor agent for human androgen-dependent and -independent prostate carcinoma cells in vitro and in vivo through the inhibition of MALT1 expression via the AR/p53/NF-κB signaling pathways.

Furthermore, MALT1 expression is closely related to the occurrence and development of multiple tumors in multiple ways. Therefore, MALT1 may be an emerging therapeutic target for a variety of cancers especially PCa.

MALT1, Th1, and Th17 cells are dysregulated, inter-correlated, and correlated with disease activity in RA patients; meanwhile, the decline of MALT1 expression can partly reflect RA treatment response and remission.

MALT1 expression is increased and positively correlates with disease severity, Th1 cells, and Th17 cells, whose high expression severs as an independent risk factor for worse RFS in AIS patients.

MALT1 enhanced NF-κB activity in prostate carcinoma cells; moreover, NF-κB induced MALT1 expression determined by reporter and immunoblot assays, implying there is a positive feedback loop between MALT1 and NF-κB. In conclusion, MALT1 is a NF-κB-induced oncogene in the human prostate carcinoma cells.

Finally, we propose future research directions to accelerate the discovery of novel MALT1 inhibitors with clinical applications. Overall, this review provides a comprehensive and systematic overview of MALT1-related research advances and serves as a theoretical basis for drug discovery and research.