A
bstract
We study aspects of the vertex operator algebra (VOA) corresponding to Argyres-Douglas (AD) theories engineered using the 6d
N
=
2
,
0
theory of type J on a punctured sphere. We denote the ...AD theories as (
J
b
k
,
Y
), where
J
b
k
and
Y
represent an irregular and a regular singularity respectively. We restrict to the ‘minimal’ case where
J
b
k
has no associated mass parameters, and the theory does not admit any exactly marginal deformations. The VOA corresponding to the AD theory is conjectured to be the W-algebra
W
k
2
d
J
,
Y
, where
k
2
d
=
−
h
+
b
b
+
k
with h being the dual Coxeter number of
J
. We verify this conjecture by showing that the Schur index of the AD theory is identical to the vacuum character of the corresponding VOA, and the Hall-Littlewood index computes the Hilbert series of the Higgs branch. We also find that the Schur and Hall-Littlewood index for the AD theory can be written in a simple closed form for
b
=
h
. We also test the conjecture that the associated variety of such VOA is identical to the Higgs branch. The M5-brane construction of these theories and the corresponding TQFT structure of the index play a crucial role in our computations.
Circular RNAs (circRNAs) exhibited important roles in Alzheimer’s disease (AD). Here, we focused on the dysregulation of hsa_circ_0049472 (circ_0049472) and potential functions in SK-N-SH cells with ...amyloid-beta peptide (Aβ) treatment in AD.
RNA expression was detected by real-time quantitative PCR. Cell viability and proliferation were measured by MTS and Edu assays. Flow cytometry was used for apoptosis detection, and cell inflammation was assessed using enzyme-linked immunosorbent assay. Target interaction was validated by dual-luciferase reporter assay and RNA immunoprecipitation assay. Protein expression and phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) pathway were examined by Immunoblotting.
Aβ treatment inhibited cell viability and proliferation of SK-N-SH cells, but enhanced apoptosis rate, apoptosis protein levels (Bcl2-associated X protein and cleaved-caspase-3) and inflammatory cytokines (interleukin −6, IL-1β, tumor necrosis factor-α). Then, circ_0049472 expression was shown to be upregulated in response to Aβ stimulation and knockdown of circ_0049472 has ameliorated Aβ-induced cell injury. Circ_0049472 was identified as a sponge for miR-22–3p, and miR-22–3p inhibition reversed the regulation of circ_0049472 knockdown in Aβ-treated cells. Furthermore, ZNF217 acted as a target of miR-22–3p and circ_0049472 could regulate ZNF217 expression via binding to miR-22–3p. Overexpression of miR-22–3p abated Aβ-induced apoptosis and inflammation via downregulating ZNF217. Furthermore, Aβ reduced proteins levels of p-PI3K and p-AKT, and this inhibition of PI3K-AKT pathway was restored by the regulation of circ_0049472/miR-22–3p/ZNF217 axis.
Circ_0049472 was involved in Aβ-induced neural injury by regulating miR-22–3p/ZNF217 axis to affect PI3K-AKT pathway. This study has discovered an innovative mechanism for AD.
•Hsa_circ_0049472 expression was upregulated with Aβ treatment.•Exhausting hsa_circ_0049472 mitigated Aβ-induced neurotoxicity, apoptosis and inflammation.•There was direct interaction between miR-22–3p and hsa_circ_0049472 or ZNF217.•Aβ-inactivated PI3K-AKT signaling pathway was restrained by silencing hsa_circ_0049472.
As the most prevalent internal modification in mammalian messenger RNA, N6‑methyladenosine (m6A) plays an important role in posttranscriptional gene regulation. METTL3 is a key component of the m6A ...methyltransferase complex and has recently been shown to play important roles in cancer development and progression. The current study was aimed to explore the function and underlying mechanism of METTL3 in ovarian cancer.
METTL3 expression was assessed by immunohistochemistry in 162 ovarian carcinoma patients. Stable cell lines with METTL3 gene overexpression or knockdown were established to investigate the function of METTL3 in ovarian cancer in vitro and in vivo.
METTL3 was frequently upregulated in ovarian carcinoma and that a high level of METTL3 was significantly associated with tumor grade (P = 0.001), pT status (P = 0.002), pN/pM status (P < 0.001), FIGO stage (P < 0.001), and overall survival rate (P < 0.001). Stable overexpression of METTL3 in the OVCAR3 and COV504 cell lines significantly increased cellular proliferation, focus formation, motility, invasion, and tumor formation in nude mice. Silencing METTL3 expression in the SKOV3 and HO-8910 cell lines with short hairpin RNA effectively inhibited its oncogenic function. Further study found that METTL3 promoted epithelial-mesenchymal transition (EMT) by upregulating the receptor tyrosine kinase AXL.
Our findings suggest that METTL3 plays very important oncogenic roles in ovarian carcinoma development and/or aggressiveness by stimulating AXL translation and EMT and that METTL3 may serve as a novel prognostic and/or therapeutic target of interest in ovarian cancer.
•METTL3 upregulation is associated with poor overall survival in ovarian carcinoma patients.•METTL3 promotes the proliferation, invasion and tumor formation of ovarian cancer cells.•METTL3 promotes epithelial to mesenchymal transition in ovarian cancer cells.•METTL3 promotes AXL translation independent of its catalytic activity.
A
bstract
We study S-duality of Argyres-Douglas theories obtained by compactification of 6d (2,0) theories of
ADE
type on a sphere with irregular punctures. The weakly coupled descriptions are given ...by the degeneration limit of auxiliary Riemann sphere with marked points, among which three punctured sphere represents isolated superconformal theories. We also discuss twisted irregular punctures and their S-duality.
Abstract
Circular RNAs (circRNAs) have been implicated in cancer progression through largely unknown mechanisms. Herein, we identify an
N
6
-methyladenosine (m
6
A) modified circRNA, circNSUN2, ...frequently upregulated in tumor tissues and serum samples from colorectal carcinoma (CRC) patients with liver metastasis (LM) and predicts poorer patient survival. The upregulated expression of circNSUN2 promotes LM in PDX metastasis models in vivo and accelerates cancer cells invasion in vitro. Importantly,
N
6
-methyladenosine modification of circNSUN2 increases export to the cytoplasm. By forming a circNSUN2/IGF2BP2/
HMGA2
RNA-protein ternary complex in the cytoplasm, circNSUN2 enhances the stability of
HMGA2
mRNA to promote CRC metastasis progression. Clinically, the upregulated expressions of circNSUN2 and
HMGA2
are more prevalent in LM tissues than in primary CRC tissues. These findings elucidate that
N
6
-methyladenosine modification of circNSUN2 modulates cytoplasmic export and stabilizes
HMGA2
to promote CRC LM, and suggest that circNSUN2 could represent a critical prognostic marker and/or therapeutic target for the disease.
Acute liver failure (ALF) is a severe liver disease caused by disruptions in the body’s immune microenvironment. In the early stages of ALF, Kupffer cells (KCs) become depleted and recruit monocytes ...derived from the bone marrow or abdomen to replace the depleted macrophages entering the liver. These monocytes differentiate into mature macrophages, which are activated in the immune microenvironment of the liver and polarized to perform various functions. Macrophage polarization can occur in two directions: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages. Controlling the ratio and direction of M1 and M2 in ALF can help reduce liver injury. However, the liver damage caused by pyroptosis should not be underestimated, as it is a caspase-dependent form of cell death. Inhibiting pyroptosis has been shown to effectively reduce liver damage induced by ALF. Furthermore, macrophage polarization and pyroptosis share common binding sites, signaling pathways, and outcomes. In the review, we describe the role of macrophage polarization and pyroptosis in the pathogenesis of ALF. Additionally, we preliminarily explore the relationship between macrophage polarization and pyroptosis, as well as their effects on ALF.
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