MiR-146a-5p plays different roles in different types of cancers. We showed that miR-146a-5p and long noncoding RNA HOTAIR were both upregulated in triple-negative breast cancer. Follow-up study ...showed that high levels of miR-146a-5p and HOTAIR in tumor tissues were closely correlated with poor survival. MiR-146a-5p and HOTAIR were positively correlated in tumor tissues. MiR-146a-5p positively regulated HOTAIR triple-negative breast cancer cells, while HOTAIR showed no regulatory effects on miR-146a-5p expression. MiR-146a-5p and HOTAIR positively regulated the migration and invasion of triple-negative breast cancer cells. In addition, HOTAIR silencing attenuated the effects of miR-146a-5p. Therefore, overexpression of miR-146a-5p may promote triple-negative breast cancer cell invasion and migration by upregulating HOTAIR.
Brain metastasis is a major cause of cancer mortality, but its molecular mechanisms are severely understudied. In addition, little is known regarding the role of m6A reader YTHDF3 in human diseases. ...Here, we show that YTHDF3 overexpression clinically correlates with brain metastases in breast cancer patients. YTHDF3 promotes cancer cell interactions with brain endothelial cells and astrocytes, blood-brain barrier extravasation, angiogenesis, and outgrow. Mechanistically, YTHDF3 enhances the translation of m6A-enriched transcripts for ST6GALNAC5, GJA1, and EGFR, all associated with brain metastasis. Furthermore, overexpression of YTHDF3 in brain metastases is attributed to increased gene copy number and the autoregulation of YTHDF3 cap-independent translation by binding to m6A residues within its own 5′ UTR. Our work uncovers an essential role of YTHDF3 in controlling the interaction between cancer cells and brain microenvironment, thereby inducing brain metastatic competence.
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•YTHDF3 overexpression clinically correlates with breast cancer brain metastases•Breast cancer brain metastases have YTHDF3 gene copy gain and autoregulation•YTHDF3 plays critical roles in multiple steps of brain metastasis cascade•YTHDF3 promotes translation of the key brain metastatic genes ST6GALNAC5 and GJA1
Chang et al. report that YTHDF3 overexpression associates with breast cancer brain metastasis and confers poor survival. Mechanistically, YTHDF3 enhances the expression of m6A-enriched transcripts that promote cancer cell-brain microenvironment interactions and brain metastasis.
Cold plasma (CP) is a non-thermal preservation technology that has been successfully used to decontaminate and extend the shelf life of aquatic products. However, the preservation effect of CP ...treatment is determined by several factors, including voltage, time, and gas compositions. Therefore, this study aimed to investigate the effects of gas composition (GasA: 10% O
, 50% N
, 40% CO
; GasB: air; GasC: 30% O
, 30% N
, 40% CO
) on the lipid oxidation of tilapia fillets treated after CP treatment. Changes in the lipid oxidation values, the percentages of fatty acids, and sensory scores were studied during 8 d of refrigerator storage. The results showed that the CP treatment significantly increased all the primary and secondary lipid oxidation values measured in this study, as well as the percentages of saturated fatty acids, but decreased the percentages of unsaturated fatty acids, especially polyunsaturated fatty acids. The lipid oxidation values were significantly increased in the GasC-CP group. After 8 d, clearly increased percentages of saturated fatty acids, a low level of major polyunsaturated fatty acids (especially linoleic (C18:2n-6)), and a decrease in the percentages of eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) were found in GasC-CP; that is, the serious oxidation of lipids was found in the high O
concentration group. In addition, the sensory score was also lower than that of the hypoxia CP group. Therefore, high O
concentrations can enhance lipid oxidation and the changes in the fatty acid concentration. Controlling the O
concentration is reasonable to limit the degree to which lipids are oxidized in tilapia after the in-package CP treatment.
•Higher contents of aldehydes, ketones, and alcohols were found in the PAW-DBD group.•Alterations in lipid profiles were studied by LC-MS-based lipidomics analyses.•130 lipid species were identified ...as DALs.•TG was the major lipid of 130 DALs.•Glycerophospholipid metabolism was the predominant metabolic pathway.
To explore the combination effects of plasma-activated water and dielectric barrier discharge (PAW-DBD) cold plasma treatment on the formation of volatile flavor and lipid oxidation in Asian sea bass (ASB), the volatile flavor compounds and lipid profiles were characterized by gas chromatography-ion mobility spectrometry and LC-MS-based lipidomics analyses. In total, 38 volatile flavor compound types were identified, and the PAW-DBD group showed the most kinds of volatile components with a significant (p < 0.05) higher content in aldehydes, ketones, and alcohols. A total of 1500 lipids was detected in lipidomics analysis, phosphatidylcholine was the most followed by triglyceride. The total saturated fatty acids content in PAW-DBD group increased by 105.02 μg/g, while the total content of unsaturated fatty acids decreased by 275.36 μg/g. It can be concluded that the PAW-DBD processing increased both the types and amounts of the volatile flavor in ASB and promoted lipid oxidation by altering lipid profiles.
A comprehensive LC-MS-based lipidomics analysis of Asian sea bass (Lates calcarifer) muscle after dielectric barrier discharge (DBD) atmospheric plasma treatment was performed. Through the analysis, ...1500 lipid species were detected, phosphatidylcholine (PC, 27.80%) was the most abundant lipid, followed by triglyceride (TG, 20.50%) and phosphatidylethanolamine (PE, 17.10%). Among them, 125 lipid species were detected and identified as differentially abundant lipids in Asian sea bass (ASB). PCA and OPLS-DA showed that ASB lipids changed significantly after DBD treatment. Moreover, glycerophospholipid metabolism was key metabolic pathways, as PC, PE, and lysophosphatidylcholine (LPC) were key lipid metabolites. The findings concerning fatty acids revealed that the saturated fatty acids (SFA) content of ASB after DBD treatment increased by 8.54%, while the content of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) decreased by 13.77% and 9.16%, respectively. Our study establishes a foundation for the lipid oxidation mechanism of ASB following DBD treatment.
A lipidomics approach based on liquid chromatography-mass spectrometry was employed to investigate alterations in lipid profiles within the muscles of Asian sea bass (ASB) (Lates calcarifer) ...post-treatment with plasms-activated water (PAW). Lipidomics studies detected 1500 diverse lipid types in ASB muscles; the phosphatidylcholine (PC) lipid subclass constituted the highest number of lipids (21.07 %), followed by triglycerides (TGs, 20.53 %) and phosphatidylethanolamine (PE, 12.73 %). Comparative analysis between PAW-treated ASB and raw ASB revealed the presence of differentially abundant lipids, with 48 lipids accumulating at high levels and 92 at low levels. Pathway enrichment analysis identified a total of seven lipid-related metabolic pathways; glycerophospholipid metabolism emerged as the predominant pathway. Furthermore, the content of saturated fatty acids in PAW-treated ASB increased from 1059.81 μg/g (raw ASB) to 1099.77 μg/g. Conversely, the content of monounsaturated and polyunsaturated fatty acids decreased from 645.81 μg/g and 875.02 μg/g to 640.80 μg/g and 825.25 μg/g, respectively. Collectively, these results indicate significant alterations in ASB lipid profiles following PAW treatment, establishing a theoretical foundation for understanding the mechanism involved in promoting lipid oxidation.
Abstract
Colorectal cancer (CRC) is one of the most lethal cancers worldwide. The expression of β-arrestin2 (β-Arr2, ARRB2) in CRC has been well investigated; however, its exact mechanism causing the ...cancer progression remains unclear. In this study, we discovered that the expression level of ARRB2 was significantly upregulated in CRC as compared to the normal tissues by employing the Cancer Genome Atlas (TCGA) data, western blot analysis, and immunohistochemistry. Furthermore, the level of ARRB2 was correlated with the patients’ overall survival by Kaplan–Meier analysis. The higher expression of ARRB2 promoted CRC cell growth, enhanced the cell motility, and blocked cell apoptosis, which is crucial for tumor growth. Lastly, the suppression of ARRB2 expression was enough to attenuate the progression of CRC induced by azoxymethane/dextran sodium sulfate. Interestingly, we also found that the knockdown of ARRB2 decreased several cancer pathways mediated by the expression of Wilms tumor 1 associated protein (WTAP), which led to the inhibition of cell proliferation and migration. Altogether, our results demonstrated that ARRB2 promoted the growth and migration of CRC cells by regulating the WTAP expression.
Insulin-like growth factor-1 (IGF-1) possesses the ability to attenuate intestinal damage and promote mucosal repair of colitis. β-Arrestins, as the scaffolding proteins of G protein-coupled ...receptors or non-G protein-coupled receptors signaling, can be involved in IGF-1–mediated signaling pathways. However, the interaction of IGF-1 and β-arrestin2 in the mucosal repair of experimental colitis remains unexplored. Ulcerative colitis was induced in β-arrestin2 wild-type mice and β-arrestin2 knockout littermates by using 3% dextran sulfate sodium for 5 days, followed by regular water consumption for 1, 2, 3, and 4 weeks to analyze the mucosal repair from experimental colitis. Disease activity index and histologic score analyses were performed. Apoptosis and proliferation were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Ki-67 staining, respectively. The expressions of β-arrestin2, phospho (p)-IGF-1R, and p-extracellular signal-regulated kinase (ERK)1/2 were examined. Furthermore, β-arrestin2 was overexpressed or altered in HCT116 cells by transfection before IGF-1 treatment in vitro . IGF-1 and β-arrestin2 expression was up-regulated in the repairing phase of experimental colitis. Targeted deletion of β-arrestin2 delayed the repair of colitis by inhibiting cell proliferation without affecting the levels of IGF-1 and p-IGF-1R. The β-arrestin2/ERK signaling pathway was involved in IGF-1–mediated mucosal repair through promoting epithelial cell and goblet cell regeneration from experimental colitis. These results indicate that IGF-1 contributes to the mucosal repair by β-arrestin2–mediated ERK signaling in experimental colitis.
Hyperactivation of transforming growth factor-β (TGF-β) signaling pathway is a common feature of hepatocellular carcinoma (HCC) progression. However, the driver factors leading to enhanced TGF-β ...activity are not well characterized. Here, we explore the mechanisms that loss of Krüppel-like factor 4 (KLF4) exacerbates oncogenic TGF-β signaling in human HCC. The expression of KLF4 and TGF-β signaling components in primary HCC and their clinicopathologic relevance and significance was evaluated by using tissue microarray and immunohistochemistry. Cellular and molecular impacts of altered KLF4 expression and TGF-β signaling were determined using immunofluorescence, western blot, reverse-transcriptase PCR, chromatin immunoprecipitation and promoter reporter assays. Loss of KLF4 expression in primary HCC closely correlated with decreased Smad7 expression, increased p-Smad2/3 expression and independently predicts reduced overall and relapse-free survival after surgery. TGF-β signaling components were expressed in most HCC cells, and activation of TGF-β signaling promoted cell migration and invasion. Enforced KLF4 expression blocked TGF-β signal transduction and inhibited cell migration and invasion via activation of Smad7 transcription, whereas deletion of its C-terminal zinc-finger domain diminished this effect. KLF4 protein physically interacts with the Smad7 promoter. Promoter deletion and point mutation analyses revealed that a region between nucleotides -15 bp and -9 bp of the Smad7 promoter was required for the induction of Smad7 promoter activity by KLF4. Our data indicate that KLF4 suppresses oncogenic TGF-β signaling by activation of Smad7 transcription, and that loss of KLF4 expression in primary HCC may contribute to activation of oncogenic TGF-β signaling and subsequent tumor progression.
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