Background: Tamoxifen resistance remains a clinical challenge for hormone receptor-positive breast cancer. Recently, dysregulations in autophagy have been suggested as a potential mechanism for tamoxifen resistance. Although the long noncoding RNA H19 is involved in various stages of tumorigenesis, its role in tamoxifen resistance remains unknown. Here, we assessed the role of H19 in the development of tamoxifenresistant breast cancer. Methods: Quantitative real-time PCR analyzed expression of H19 in tamoxifen-resistant breast cancer tissues. Knockdown of H19 was used to assess the sensitivity to tamoxifen in vitro and in vivo. Both knockdown and overexpression of H19 were used to analyze the status of autophagy. Real-time quantitative methylationspecific polymerase chain reaction, chromatin immunoprecipitation, immunofluorescence, and Western blot were used to explore the tamoxifen resistance mechanism of H19. Results: In this study, we observed that the expression of H19 was substantially upregulated in tamoxifen-resistant breast cancer cell line and tumor tissues, and knockdown of H19 enhanced the sensitivity to tamoxifen both in vitro and in vivo. Furthermore, knockdown of H19 significantly inhibited autophagy in MCF7 tamoxifen-resistant (MCF7/ TAMR) cells. Conversely, overexpression of H19 promoted autophagy. Interestingly, overexpression of H19 in MCF7 tamoxifen-sensitive cells could recapitulate tamoxifen resistance. Moreover, an increase in methylation in the promoter region of Beclin1 was observed in MCF7/TAMR-shH19 cells. In the double knockdown groups, both shH19+shSAHH and shH19+shDNMT3B rescued the Beclin1 promoter region methylation levels and reactivated autophagy functions. A chromatin immunoprecipitation assay further validated that DNMT3B binds to the Beclin1 promoter region and the knockdown of H19 increases this binding. Conclusions: Our findings demonstrate that H19 induces autophagy activation via the H19/SAHH/DNMT3B axis, which could contribute to tamoxifen resistance in breast cancer.
Accumulating evidence suggests that placenta-specific 8 (PLAC8) plays an important role in normal cellular process and human diseases, including multiple types of human tumors, and its role is highly relied upon in cellular and physiologic contexts. However, there are no reports on its expression profile and biological roles during lung cancer development. In the current study, both the clinical implications and biological effects of PLAC8 in lung cancer (LC) progression were investigated, and we identified and described the novel Krüppel-like factor 4 (KLF4)/PLAC8 regulatory pathway in cancer progression. Elevated PLAC8 levels were positively correlated with tumor size, histological grade, and tumor node metasis (TNM) stage, and LC patients with high PLAC8 expression suffered poor outcomes. In vitro and in vivo assays further revealed that endogenous PLAC8 promoted cell proliferation and tumor formation. We also found downregulated PLAC8 protein in several LC cell lines following the induction of KLF4, and immunohistochemistry analysis of LC tissues by microarray indicated a potential inverse correlation between PLAC8 and KLF4 expression. Luciferase reporter analysis and chromatin immunoprecipitation assays determined that KLF4 negatively regulated PLAC8 promoter activity via directly binding to the promoter region. Furthermore, the growth inhibition resulting from KLF4 overexpression was partially rescued by ectopic PLAC8 expression. Together, our data uncovered a previously unidentified role of PLAC8 as a central mediator in LC progression. PLAC8 was transcriptionally repressed by KLF4, and the novel KLF4/PLAC8 axis may act as a promising candidate target for LC diagnosis and therapy.
Roasted fish fillet (Fig.1) represents a popular snack food in China and a preliminary analysis of the label found only fish common names, without any reference to a particular species (Table 1). Since there is still not a harmonization around the definition of these common names in China, retailers are thus induced to mislabel roasted fish fillet products for lucrative profits. This study used direct sequencing method based on fragments of 16S rRNA gene and subsequent BLAST analysis to investigate the species composition of roasted fish fillet products circulated on Chinese market. An exclusive criterion was defined to determine the labeling accuracy and only the identified species beyond the expected family was considered as mislabeling. Results highlighted an inadequate enforcement of relative rules and a high mislabeling rate of 75.9%. A worse fact was the identification of multiple fish species not only from several packages under the same common name, but also from several specimens belonging to a single package. In order to protect the consumers from economic loss and even health risk, we recommended the amendments to the existing legislations and the compilation of list of acceptable market names for fish species in China.
Cyclophosphamide (CTX) is a widely used anticancer drug with severe nephrotoxicity. The pentadecapeptide (RVAPEEHPVEGRYLV) from Cyclina sinensis (SCSP) has been shown to affect immunity and to protect the liver. Hence, the purpose of this study was to investigate the ameliorating effect of SCSP on CTX-induced nephrotoxicity in mice. We injected male ICR mice with CTX (80 mg/kg·day) and measured the nephrotoxicity indices, levels of antioxidant enzymes, malondialdehyde (MDA), inflammatory factors, as well as the major proteins of the NF-κB and apoptotic pathways. Cyclophosphamide induced kidney injury; the levels of kidney-injury indicators and cytokines recovered remarkably in mice after receiving SCSP. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) increased, while there was a significant decrease in MDA levels. The kidney tissue damage induced by CTX was also repaired to a certain extent. In addition, SCSP significantly inhibited inflammatory factors and apoptosis by regulating the NF-κB and apoptotic pathways. Our study shows that SCSP has the potential to ameliorate CTX-induced nephrotoxicity and may be used as a therapeutic adjuvant to ameliorate CTX-induced nephrotoxicity.
Bioactive peptides isolated from marine organisms have shown to have potential anti-inflammatory effects. This study aimed to investigate the intestinal protection effect of low molecular peptides (Mw < 1 kDa) produced through enzymatic hydrolysis of tuna processing waste (tuna bioactive peptides (TBP)) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in BALB/c mice. Here, we randomly divided twenty-four male BALB/c mice into four groups: (i) normal (untreated), (ii) DSS-induced model colitis, (iii) low dose TBP+DSS-treated (200 mg/kg/d), and (iv) high dose TBP+DSS-treated groups (500 mg/kg/d). The results showed that TBP significantly reduced mice weight loss and improved morphological and pathological characteristics of colon tissues. In addition, it increased the activities of antioxidant enzymes (SOD and GSH-Px) and decreased inflammatory factors (LPS, IL-6, and TNF-α) expression. TBP increased the gene expression levels of some tight junction (TJ) proteins. Moreover, TBP increased the short-chain fatty acids (SCFAs) levels and the diversity and imbalance of intestinal flora. Therefore, TBP plays some protective roles in the intestinal tract by enhancing antioxidant and anti-inflammatory abilities of the body, improving the intestinal barrier and metabolic abnormalities, and adjusting intestinal flora imbalance.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.