Luteolin (LTL) exerts remarkable tumor suppressive activity on various types of cancers, including non-small cell lung cancer (NSCLC). However, it is not completely understood whether the mechanism of its action against NSCLC is related to microRNAs (miRNAs). In the present study, we investigated the anti-tumor effects of LTL on NSCLC in vitro and in vivo. The results revealed that LTL could inhibit cell proliferation and induce apoptosis in both A549 and H460 cells. In a H460 xenograft tumor model of nude mice, LTL significantly suppressed tumor growth, inhibited cell proliferation, and induced apoptosis. miRNA microarray and quantitative PCR (qPCR) analysis indicated that miR-34a-5p was dramatically upregulated upon LTL treatment in tumor tissues. Furthermore, MDM4 was proved to be a direct target of miR-34a-5p by luciferase reporter gene assay. LTL treatment was associated with increased p53 and p21 protein expressions and decreased MDM4 protein expression in both NSCLC cells and tumor tissues. When miR-34a-5p was inhibited in vitro, the protein expressions of Bcl-2 and MDM4 were recovered, while that of p53, p21, and Bax were attenuated. Moreover, caspase-3 and caspase-9 activation induced by LHL treatment in vitro were also suppressed by miR-34a-5p inhibition. Overall, LTL could inhibit tumorigenesis and induce apoptosis of NSCLC cells by upregulation of miR-34a-5p via targeting MDM4. These findings provide novel insight into the molecular functions of LTL that suggest its potential as a therapeutic agent for human NSCLC.

BackgroundInsulin-like growth factor 2 mRNA binding protein 3 (IMP3) is expressed in metastatic and a subset of primary renal cell carcinoma (RCC). However, the role of IMP3 in RCC progression was poorly understood. We aim to uncover the mechanism of IMP3 in regulating clear cell RCC (CCRCC) progression and validate the prognostic significance of IMP3 in localized CCRCC.MethodsCaki-1 cells stably overexpressing IMP3 and Achn cells with knockdown of IMP3 were analyzed for cell migration and invasion by Transwell assay. RNA-seq was used to profile gene expression in IMP3-expressing Caki-1 cells. A cohort of 469 localized CCRCC patients were examined for IMP3 expression by immunohistochemistry using tumor tissue array.ResultsIMP3 promoted Caki-1 cell migration and invasion, whereas knockdown of IMP3 by RNAi inhibited Achn cell migration and invasion. Enhanced IMP3 expression activated NF-кB pathway and through which, it functioned in promoting the RCC cell migration. IMP3 expression in localized CCRCC was found to be associated with higher nuclear grade, higher T stage, necrosis and sarcomatoid differentiation (p< 0.001). Enhanced IMP3 expression was correlated with shorter recurrence-free and overall survivals. Multivariable analysis validated IMP3 as an independent prognostic factor for localized CCRCC patients.ConclusionIMP3 promotes RCC cell migration and invasion by activation of NF-кB pathway. IMP3 is validated to be an independent prognostic marker for localized CCRCC.

Heteroatom doping can endow MXenes with various new or improved electromagnetic, physicochemical, optical, and structural properties. This greatly extends the arsenal of MXenes materials and their potential for a spectrum of applications. This article comprehensively and critically discusses the syntheses, properties, and emerging applications of the growing family of heteroatom‐doped MXenes materials. First, the doping strategies, synthesis methods, and theoretical simulations of high‐performance MXenes materials are summarized. In order to achieve high‐performance MXenes materials, the mechanism of atomic element doping from three aspects of lattice optimization, functional substitution, and interface modification is analyzed and summarized, aiming to provide clues for developing new and controllable synthetic routes. The mechanisms underlying their advantageous uses for energy storage, catalysis, sensors, environmental purification and biomedicine are highlighted. Finally, future opportunities and challenges for the study and application of multifunctional high‐performance MXenes are presented. This work could open up new prospects for the development of high‐performance MXenes.

As a subset of pattern recognition receptors (PRRs), C-type lectin-like receptors (CLRs) are mainly expressed by myeloid cells as both transmembrane and soluble forms. CLRs recognize not only pathogen associated molecular patterns (PAMPs), but also damage-associated molecular patterns (DAMPs) to promote innate immune responses and affect adaptive immune responses. Upon engagement by PAMPs or DAMPs, CLR signaling initiates various biological activities in vivo, such as cytokine secretion and immune cell recruitment. Recently, several CLRs have been implicated as contributory to the pathogenesis of intestinal inflammation, which represents a prominent risk factor for colorectal cancer (CRC). CLRs function as an interface among microbiota, intestinal epithelial barrier and immune system, so we firstly discussed the relationship between dysbiosis caused by microbiota alteration and inflammatory bowel disease (IBD), then focused on the role of CLRs signaling in pathogenesis of IBD (including Mincle, Dectin-3, Dectin-1, DCIR, DC-SIGN, LOX-1 and their downstream CARD9). Given that CLRs mediate intricate inflammatory signals and inflammation plays a significant role in tumorigenesis, we finally highlight the specific effects of CLRs on CRC, especially colitis-associated cancer (CAC), hoping to open new horizons on pathogenesis and therapeutics of IBD and CAC.