Applying differentially expressed genes (DEGs) to identify feasible biomarkers in diseases can be a hard task when working with heterogeneous datasets. Expression data are strongly influenced by technology, sample preparation processes, and/or labeling methods. The proliferation of different microarray platforms for measuring gene expression increases the need to develop models able to compare their results, especially when different technologies can lead to signal values that vary greatly. Integrative meta-analysis can significantly improve the reliability and robustness of DEG detection. The objective of this work was to develop an integrative approach for identifying potential cancer biomarkers by integrating gene expression data from two different platforms. Pancreatic ductal adenocarcinoma (PDAC), where there is an urgent need to find new biomarkers due its late diagnosis, is an ideal candidate for testing this technology. Expression data from two different datasets, namely Affymetrix and Illumina (18 and 36 PDAC patients, respectively), as well as from 18 healthy controls, was used for this study. A meta-analysis based on an empirical Bayesian methodology (ComBat) was then proposed to integrate these datasets. DEGs were finally identified from the integrated data by using the statistical programming language R. After our integrative meta-analysis, 5 genes were commonly identified within the individual analyses of the independent datasets. Also, 28 novel genes that were not reported by the individual analyses ('gained' genes) were also discovered. Several of these gained genes have been already related to other gastroenterological tumors. The proposed integrative meta-analysis has revealed novel DEGs that may play an important role in PDAC and could be potential biomarkers for diagnosing the disease.

/pdf/integrative-multi-platform-meta-analysis-of-gene-expression-32m5nk6nrk.pdf

Integrative multi-platform meta-analysis of gene expression profiles in pancreatic ductal adenocarcinoma patients for identifying novel diagnostic biomarkers.

Purpose Anoctamin6 (ANO6) plays a crucial role in several cancers, whereas the specific role of ANO6 in glioblastoma is unclear. Methods Kaplan-Meier survival analysis was used to analysis the correlation between ANO6 and survival rate of patients with glioblastoma. Univariate Cox regression analysis was used to analysis the correlation among ANO6 expression level,and age, gender, WHO and overall survival rate. Immunohistocemical technique, RT-PCR and western blot were used to dected the ANO6 expression. CCK8, colony formation and transwell were used to detected cell viability, cell proliferation and cell invasion in glioblastoma cells transfected with sh-ANO6 and ANO6 overexpression. In addition, after SHG-44 cells trasfected with ANO6 overexpression were ERK inhibitor (PD98059), CCK8, colony formation and transwell were used to detected cell viability, cell proliferation and cell invasion. Western blot was used to detected ERK protein level and the phosphorylation level of ERK in T89G and U87MG cells tranfected wih sh-ANO6. Results The results indicated that the ANO6 expression level was significantly associated with patients' age and tumor stage. Univariate Cox regression analysis showed that the ANO6 expression level, age, gender and tumor stage were not related to the overall survival rate. ANO6 inhibition significantly suppressed the viability, invasion and the ability of colony formation in glioma cells, while ANO6 overexpression led to the opposite results in SHG-44 cells. ANO6 knockdown strongly inhibits the phosphorylation level and nuclear translocation of extracellular signal-regulated kinase (ERK) protein to inhibit ERK signaling. ERK inhibitor significantly decreased the cell proliferation and invasion in SHG-44 cells transfected with sh-ANO6. Conclusion This study revealed that ANO6 activited ERK signaling pathway through promoting the nuclear translocation of ERK to increase the proliferation and invasion of glioblastoma cells.

/pdf/ano6-promotes-cell-proliferation-and-invasion-in-glioma-4pywjmalg6.pdf

ANO6 promotes cell proliferation and invasion in glioma through regulating the ERK signaling pathway.

Sirtuins (SIRT1-SIRT7), a family of nicotinamide adenine dinucleotide (NAD+)-dependent enzymes, are key regulators of life span and metabolism. In addition to acting as deacetylates, some sirtuins have the properties of deacylase, decrotonylase, adenosine diphosphate (ADP)-ribosyltransferase, lipoamidase, desuccinylase, demalonylase, deglutarylase, and demyristolyase. Mitochondrial dysfunction occurs early on and acts causally in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Sirtuins are implicated in the regulation of mitochondrial quality control, which is highly associated with the pathogenesis of neurodegenerative diseases. There is growing evidence indicating that sirtuins are promising and well-documented molecular targets for the treatment of mitochondrial dysfunction and neurodegenerative disorders by regulating mitochondrial quality control, including mitochondrial biogenesis, mitophagy, mitochondrial fission/fusion dynamics, and mitochondrial unfolded protein responses (mtUPR). Therefore, elucidation of the molecular etiology of sirtuin-mediated mitochondrial quality control points to new prospects for the treatment of neurodegenerative diseases. However, the mechanisms underlying sirtuin-mediated mitochondrial quality control remain obscure. In this review, we update and summarize the current understanding of the structure, function, and regulation of sirtuins with an emphasis on the cumulative and putative effects of sirtuins on mitochondrial biology and neurodegenerative diseases, particularly their roles in mitochondrial quality control. In addition, we outline the potential therapeutic applications for neurodegenerative diseases of targeting sirtuin-mediated mitochondrial quality control through exercise training, calorie restriction, and sirtuin modulators in neurodegenerative diseases. 

http://www.aginganddisease.org/EN/PDF/10.14336/AD.2022.1123

Sirtuins at the Crossroads between Mitochondrial Quality Control and Neurodegenerative Diseases: Structure, Regulation, Modifications, and Modulators

The canonical Wnt/β-catenin pathway is involved in diverse cancer development mechanisms, such as proliferation, migration, and invasion. However, its role in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. We investigated whether the canonical Wnt/β-catenin signaling pathway acts as a controller of invasion and lymph node metastasis (LNM) in HNSCC. Loss of function experiments against the canonical Wnt/β-catenin pathway were conducted to evaluate its invasive and metastatic role in HNSCC cells. Slug was evaluated as a downstream protein in canonical Wnt/β-catenin-mediated invasion. In addition, canonical Wnt/β-catenin and Slug expression levels were examined in 119 HNSCC tissue samples to study the relevance of these proteins in LNM and prognosis of patients post-treatment. In vitro suppression of β-catenin expression led to decreased migration and invasion of HNSCC cells. Using an in vivo mouse orthotopic LNM model, a decrease in LNM was observed with mitigated β-catenin expression. Slug expression upregulation mediates invasion and LNM by the canonical Wnt/β-catenin pathway. Simultaneous expression of β-catenin and Slug is the major predictive factor of LNM and survival rate in patients with HNSCC. In conclusion, the canonical Wnt/β-catenin/Slug signaling axis significantly contributes to cancer cell invasion and LNM. Its blockade may be a treatment strategy for LNM and tumor recurrence in HNSCC.

Wnt/β-catenin/Slug pathway contributes to tumor invasion and lymph node metastasis in head and neck squamous cell carcinoma

Phospholipid scramblase 1 (PLSCR1) is the most studied protein of the scramblase family. Originally, it was identified as a membrane protein involved in maintaining plasma membrane asymmetry. However, studies conducted over the past few years have shown the involvement of PLSCR1 in several other cellular pathways. Indeed, PLSCR1 is not only embedded in the plasma membrane but is also expressed in several intracellular compartments where it interacts with a diverse repertoire of effectors, mediators, and regulators contributing to distinct cellular processes. Although most PLSCR1 interactors are thought to be cell-type specific, PLSCR1 often exerts its regulatory functions through shared mechanisms, including the trafficking of different molecules within intracellular vesicles such as endosomes, liposomes, and phagosomes. Intriguingly, besides endogenous proteins, PLSCR1 was also reported to interact with exogenous viral proteins, thereby regulating viral uptake and spread. This review aims to summarize the current knowledge about the multiple roles of PLSCR1 in distinct cellular pathways. Video Abstract. 

/pdf/phospholipid-scramblase-1-a-protein-with-multiple-functions-76zfugfy.pdf

Phospholipid scramblase 1: a protein with multiple functions via multiple molecular interactors

Background
Membrane-bound phospholipid scramblase 1 (PLSCR1) is involved in both lipid trafficking and cell signaling. Previously, we showed that PLSCR1 is overexpressed in many colorectal carcinomas (CRCs). In the present study, we investigated the tumorigenic role of PLSCR1 in CRC and suggest that it is a potential therapeutic target.

/pdf/blockade-of-phospholipid-scramblase-1-with-its-n-terminal-9m5tm58nch.pdf

Blockade of phospholipid scramblase 1 with its N-terminal domain antibody reduces tumorigenesis of colorectal carcinomas in vitro and in vivo

Sirtuin 3 (SIRT3) deacetylase is a key regulator for chemoresistance in acute myeloid leukemia (AML) cells due to its capability of modulating mitochondrial metabolism and reactive oxygen species (ROS). SIRT3 is de-SUMOylated by SUMO-specific peptidase 1 (SENP1), which enhances its deacetylase activity. Therefore, dysregulation of SIRT3 SUMOylation may lead to fortified chemoresistance in AML. Indeed, SIRT3 de-SUMOylation was induced by chemotherapeutic agents, which in turn, exacerbated resistance against chemotherapies in AML by activating SIRT3 via preventing its proteasome degradation. Furthermore, RNA-seq revealed that expression of a collection of genes was altered by SIRT3 de-SUMOylation including inhibition of transcription factor Hes Family BHLH Transcription Factor 1 (HES1), a downstream substrate of Notch1 signaling pathway, leading to increased fatty acids oxidation (FAO). Moreover, the SENP1 inhibitor momordin-Ic or HES1 overexpression synergized with cytarabine to eradicate AML cells in vitro and in xenograft mouse models. In summary, the current study revealed a novel role of SIRT3 SUMOylation in the regulation of chemoresistance in AML via HES1-dependent FAO and provided a rationale for SIRT3 SUMOylation and FAO targeted interventions to improve chemotherapies in AML.

/pdf/dysregulation-of-sirt3-sumoylation-confers-aml-1dt4w9z7.pdf

Dysregulation of SIRT3 SUMOylation Confers AML Chemoresistance via Controlling HES1-Dependent Fatty Acid Oxidation

Differences in Pharmacokinetic and Histopathological Effects of Five Drug-Coated Balloons: An Experimental Study in Rabbit.

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Blockade of phospholipid scramblase 1 with its N-terminal domain antibody reduces tumorigenesis of colorectal carcinomas in vitro and in vivo

Dysregulation of SIRT3 SUMOylation Confers AML Chemoresistance via Controlling HES1-Dependent Fatty Acid Oxidation

Differences in Pharmacokinetic and Histopathological Effects of Five Drug-Coated Balloons: An Experimental Study in Rabbit.