<p>miR-423 Promotes Breast Cancer Invasion by Activating NF-κB Signaling</p>

Abstract

Breast cancer has become the most common malignancy among women worldwide; therefore, novel diagnostic and prognostic markers and therapeutic targets are urgently required. NF-κB signaling plays a pivotal role in enhancing breast cancer malignant phenotypes, especially cancer invasion and metastasis, which is the main cause of death in cancer patients. TNIP2, an important inhibitor of the NF-κB pathway, is known to involve a negative feedback loop of the NF-κB signaling cascade and to regulate tumor aggressiveness in various cancer types. However, the mRNA level of TNIP2 is barely altered in breast cancer; thus, the mechanism that regulates TNIP2 in breast cancer still needs to be elucidated. Methods: We analyzed the expression and prognosis of miR-423 in a TCGA BRCA miRNA cohort and in clinical specimens. We detected the invasive capacity through a Matrigel-coated Transwell penetration assay, a three-dimensional (3D) spheroid invasion assay and a wound healing assay. Then, we applied luciferase assays, real-time PCR assays and Western blotting to further study the mechanism. Results: In this study, analysis of the TCGA BRCA miRNA cohort and clinical specimens demonstrated that miR-423 was upregulated in human breast cancers and was positively correlated with clinical stage, poor overall survival and metastasis classification. Moreover, the invasiveness of breast cancer cells was enhanced by ectopic expression of miR-423 and inhibited by miR-423 downregulation. Mechanistically, upregulation of miR-423 led to activation of the NF-κB signaling pathway and elevated expression of snail and twist, while repression of miR-423 inhibited this pathway. Furthermore, the results indicated that TNIP2 is a target gene of miR-423, and suppression of TNIP2 resulted in increased invasiveness in miR-423-silenced cells. Conclusion: Our results suggest that miR-423 is a crucial factor that enhances breast cancer cell invasion through the NF-κB signaling pathway and shed light on miR-423 as a promising prognostic and therapeutic marker for metastatic breast cancer.

Carvacrol, Thymol, and Garlic Essential Oil Promote Skin Innate Immunity in Gilthead Seabream (Sparus aurata) Through the Multifactorial Modulation of the Secretory Pathway and Enhancement of Mucus Protective Capacity

“…In accordance, genes that are activated in response to the pro-inflammatory cytokine TNF, such the TNF Alpha Induced Protein 2 (tnfaip2) and TNFAIP3-Interacting Protein 2 (tnip2) were also up-regulated by the phytogenics in our study. The last inhibits the NF-kB pathway activation (82), negatively regulating the transcription of other pro-inflammatory cytokines and, consequently, controlling the inflammatory response. Thus, such response could be intimately related with the role of AIMP1 in dermal fibroblast proliferation and wound repair (83).…”

A Bioactive Extract Rich in Triterpenic Acid and Polyphenols from Olea europaea Promotes Systemic Immunity and Protects Atlantic Salmon Smolts Against Furunculosis

“…Last but not least, the tumor necrosis factor alpha-induced protein 3 ( tnfaip3 ) was also upregulated by the AQUOLIVE ® diet. TNFAIP3 is a zinc finger domain-containing protein, which is recognized to be a negative regulator of NF-κB signaling ( 93 ), thereby negatively regulating the transcription of other pro-inflammatory cytokines and, consequently, controlling the inflammatory response. Therefore, the present results suggest a hypothesis that the tested feed additive promoted an immune homeostatic effect.…”

Genetic Variation in MicroRNA-423 Promotes Proliferation, Migration, Invasion, and Chemoresistance in Breast Cancer Cells

“…In addition, Xia et al [ 47 ] reported that miR-423 acts as an oncogene to promote tumor cell proliferation and migration, inhibiting ZFP36 expression via the Wnt/β-catenin signaling pathway of BC cells. Furthermore, Dai et al (2020) [ 48 ] demonstrated that miR-423 upregulation enhances BC cell invasion through the NF-κβ signaling pathway.…”