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Yan Yang, Caiyu Jiang, Yang Yang, Lu Guo, Jiang Huang, Xingren Liu, Chi Wu, Jun Zou
Drug resistance is an important factor leading to the recurrence and metastasis of Non-Small Cell Lung Cancer (NSCLC). Long non-coding RNAs (LncRNAs) play important roles in drug resistance of tumor cells. The aim of our study was to investigate the mechanism of LncRNA-HOTAIR in regulating drug resistance of NSCLC cells. Our data indicated that HOTAIR was overexpressed in NSCLC cell lines. Silencing of HOTAIR decreased cell proliferation and increased apoptosis of NSCLC cells (A549). Besides that, HOTAIR shRNA transfection suppressed drug resistance of A549 cells to Crizotinib by more effectively inhibiting cell viability and promoting apoptosis compared with HOTAIR scramble group...
February 19, 2018: Biochemical and Biophysical Research Communications
Cong Yan, Huanhuan Huo, Cuiwei Yang, Tao Zhang, Yuanyuan Chu, Yanfen Liu
Ubiquitination modification has been shown to play a key role in autophagy. Increasing studies reported the involvement of de-ubiquitinating enzymes (DUBs) in autophagy pathway. To systematically search how DUBs manipulate autophagy, we utilized a double fluorescence tagged LC3 stable HeLa cell line, and did a genome wide screen of 55 human DUBs which is about 60% coverage of the DUB family. We found a bunch of DUBs have impact on autophagy by either changing the LC3 puncta formation or the autophagy flux. One of them, Ubiquitin C-Terminal Hydrolase L1 (UCHL1) correlated to Parkinson's disease, strongly affects autophagy by inhibiting autophagosome formation...
February 17, 2018: Biochemical and Biophysical Research Communications
Prashanta Kumar Panda, Prajna Paramita Naik, Prakash P Praharaj, Biswa Ranjan Meher, Piyush Kumar Gupta, Rama S Verma, Tapas K Maiti, Muthu K Shanmugam, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Gautam Sethi, Rajesh Agarwal, Sujit K Bhutia
Eradicating cancer stem cells (CSCs) in colorectal cancer (CRC) through differentiation therapy is a promising approach for cancer treatment. Our retrospective tumor-specimen analysis elucidated alteration in the expression of bone morphogenetic protein 2 (BMP-2) and β-catenin during the colon cancer progression, indicating that their possible intervention through "forced differentiation" in colon cancer remission. We reveal that Abrus agglutinin (AGG) induces the colon CSCs differentiation, enhancing sensitive to the anticancer therapeutics...
February 19, 2018: Molecular Carcinogenesis
Sijia Wang, Aya Kobeissi, Ying Dong, Nihal Kaplan, Wending Yang, Congcong He, Kang Zeng, Han Peng
We have shown that microRNAs-103 and -107(miRs-103/107) positively regulate end-stage autophagy via ensuring dynamin activity in cultured keratinocytes. Most work in end-stage autophagy has been conducted using in vitro model systems. In vivo regulation of end-stage autophagy in epidermis remains unknown. Here, we used antagomirs to subcutaneously knock-down miR-107 in the skin; conversely, we delivered miR-107 mimic subcutaneously via in vivo transfection to increase this miRNA. We found that antagomir-107 treatment in epidermis: (i) depleted endogenous miR-107; (ii) increased GFP-LC3 puncta in epidermal basal layers of GFP-LC3 transgenic mice, indicative of an accumulation of autophagosomes; (iii) inhibited LC3 turnover and increased p62, suggesting an inhibition of autophagy flux; and (iv) increased phosphorylated dynamin (p-dynamin, an inactive form), a key enzyme in end-stage autophagy...
February 13, 2018: Journal of Investigative Dermatology
Collin Matsumoto, Yan Jiang, Jacqueline Emathinger, Pearl Quijada, Nathalie Nguyen, Andrea De La Torre, Maryam Moshref, Jonathan Nguyen, Aimee B Levinson, Minyoung Shin, Mark A Sussman, Nirmala Hariharan
Aging severely limits myocardial repair and regeneration. Delineating the impact of age-associated factors such as short telomeres is critical to enhance the regenerative potential of cardiac progenitor cells (CPCs). We hypothesized that short telomeres activate p53 and induce autophagy to elicit the age-associated change in CPC fate. We isolated CPCs and compared mouse strains with different telomere lengths for phenotypic characteristics of aging. Wild mouse strain Mus musculus castaneus (CAST) possessing short telomeres exhibits early cardiac aging with cardiac dysfunction, hypertrophy, fibrosis and senescence, as compared to common lab strains FVB and C57 bearing longer telomeres...
February 14, 2018: Stem Cells
Woom-Yee Bae, Jae-Sun Choi, Joo-Won Jeong
Cinnamic aldehyde (CA), a key flavor compound in cinnamon essential oil, has been identified as an anti-oxidant, anti-angiogenic, and anti-inflammatory material. Recently, the neuroprotective effects of CA have been reported in various neurodegenerative disorders, including Parkinson's disease (PD). In neurons, autophagy is tightly regulated, and consequently, the dysregulation of autophagy may induce neurodegenerative disorders. In the present study, we found that the selective dopaminergic neuronal death in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models was prevented by CA...
February 12, 2018: International Journal of Molecular Sciences
Lei Tian, Zhifeng Zhao, Ling Xie, JinPeng Zhu
Gastric cancer is a prevalent cancer and chemotherapy is a main treatment for patients. Docetaxel is commonly used as a chemotherapeutic drug for gastric cancer patients. With the increasing emergence of docetaxel resistance, exploring the mechanism of chemoresistance may improve prognosis of patients. In this study, we found that overexpressed miR-361-5p suppressed chemoresistance to docetaxel of gastric cancer cells (SGC-7901, MKN-28) by decreasing IC 50 values of docetaxel while increasing cell apoptosis rate, especially in docetaxel resistant SGC-7901 cells...
January 12, 2018: Oncotarget
Robert McCoy Vernon, Paul Andrew Chong, Brian Tsang, Tae Hun Kim, Alaji Bah, Patrick Farber, Hong Lin, Julie Deborah Forman-Kay
Protein phase separation is implicated in formation of membraneless organelles, signaling puncta and the nuclear pore. Multivalent interactions of modular binding domains and their target motifs can drive phase separation. However, forces promoting the more common phase separation of intrinsically disordered regions are less understood, with suggested roles for multivalent cation-pi, pi-pi, and charge interactions and the hydrophobic effect. Known phase-separating proteins are enriched in pi-orbital containing residues and thus we analyzed pi-interactions in folded proteins...
February 9, 2018: ELife
Aylia Mohammadi, Orlaith B Kelly, Melissa Filice, Boyko Kabakchiev, Michelle I Smith, Mark S Silverberg
Background and Aims: MicroRNAs (miRNAs) have emerged as important regulators in inflammatory bowel disease (IBD). This study investigated differential expression of miRNAs across clinical phenotypes in a well-characterized cohort of IBD patients and healthy controls (HCs). Methods: A cohort with Crohn's disease (CD), ulcerative colitis (UC), and HC was prospectively accrued. Total RNA was extracted from peripheral blood mononuclear cells for all subjects. MiRNA expression was measured using NanoString Technologies...
February 6, 2018: Journal of Crohn's & Colitis
Benedikt Junglas, Dirk Schneider
While Vipp1 (also known as IM30) clearly is essential for proper biogenesis of thylakoid membranes in chloroplasts and cyanobacteria, the exact function of Vipp1/IM30 still remains unclear. The recent in vivo study of Gutu et al. now demonstrates that Vipp1/IM30 forms localized puncta specifically at highly curved membrane regions at the cell periphery. These Vipp1/IM30 puncta were found being highly dynamic under normal growth conditions, while it has recently been shown that they stably associate with membranes under high-light conditions...
February 8, 2018: Molecular Microbiology
Pooja Jadiya, Snober S Mir, Aamir Nazir
The accumulation of aggregate-prone proteins is a major representative of many neurological disorders, including Parkinson's disease (PD) wherein the cellular clearance mechanisms, such as the ubiquitin-proteasome and autophagy pathways are impaired. PD, known to be associated with multiple genetic and environmental factors, is characterized by the aggregation of α-synuclein protein and loss of dopaminergic neurons in midbrain. This disease is also associated with other cardiovascular ailments. Herein, we report our findings from studies on the effect of hyper and hypo-osmotic induced toxicity representing hyper and hypotensive condition as an extrinsic epigenetic factor towards modulation of Parkinsonism, using a genetic model Caenorhabditis elegans (C...
February 2, 2018: Cellular Signalling
Dani L Webber, Amanda Choo, Laura J Hewson, Paul J Trim, Marten F Snel, John J Hopwood, Robert I Richards, Kim M Hemsley, Louise V O'Keefe
Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder resulting from the deficit of the N-sulfoglucosamine sulfohydrolase (SGSH) enzyme that leads to accumulation of partially-degraded heparan sulfate. MPS IIIA is characterized by severe neurological symptoms, clinically presenting as Sanfilippo syndrome, for which no effective therapy is available. The lysosomal SGSH enzyme is conserved in Drosophila and we have identified increased levels of heparan sulfate in flies with ubiquitous knockdown of SGSH/CG14291...
February 1, 2018: Experimental Neurology
Feng Gu, Isabel Parada, Tao Yang, Frank M Longo, David A Prince
Post-traumatic epilepsy is one of the most common and difficult to treat forms of acquired epilepsy worldwide. Currently, there is no effective way to prevent post-traumatic epileptogenesis. It is known that abnormalities of interneurons, particularly parvalbumin-containing interneurons, play a critical role in epileptogenesis following traumatic brain injury. Thus, enhancing the function of existing parvalbumin interneurons might provide a logical therapeutic approach to prevention of post-traumatic epilepsy...
February 2, 2018: Neurobiology of Disease
Zhenjun Huang, Weilun Fang, Weihua Liu, Li Wang, Bin Liu, Shiming Liu, Shaojun Liu
Aspirin not only reduces the incidence of hepatocellular carcinoma (HCC) but also plays a synergistic role with chemotherapy for HCC treatment. However, the underlying mechanisms remain incompletely elucidated. Given that autophagy triggers cancer cell death, the present study examined the autophagic effect of aspirin on HCC cells. Results showed that aspirin increased LC3II/LC3I ratio, decreased p62 expression, and enhanced autophagic flux (autophagosome and autolysosome puncta) in Hep3B, HepG2, or SMMC-7721 cells, reflecting the autophagy of HCC cells...
January 31, 2018: European Journal of Pharmacology
Han Wang, Hua Wang, En-Yu Liang, Li-Xia Zhou, Zhan-Ling Dong, Ping Liang, Qi-Fang Weng, Mo Yang
Cardiac toxicity has been the major concern when using doxorubicin (DOX) in cancer therapy. Thrombopoietin (TPO) protects cardiac cells from DOX-induced cell damage; however, its molecular mechanism remains exclusive. The anti-autophagic and anti-apoptotic effects of TPO upon DOX treatment were studied in the cardiac H9C2 cell line, with bafilomycin A1 treatment as a positive control for autophagy inhibition. Cell viability was measured by Cell Counting Kit-8 assay in different treatment groups. The mRNA and/or protein levels of apoptotic markers and autophagy-associated factors were detected...
January 2018: Oncology Letters
Yusuke Okada, Taku Watanabe, Toru Shoji, Kyoko Taguchi, Naohisa Ogo, Akira Asai
Dimerization in signal transduction is a dynamically regulated process and a key regulatory mechanism. Signal transducer and activator of transcription 3 (STAT3) dimerizes after tyrosine phosphorylation upon cytokine stimulation. Because only the STAT3 dimer possesses the trans-activation activity, dimerization is an indispensable process for cytokine signaling. Here we report the detection of dynamic STAT3 dimerization in living cells using the homoFluoppi system. This method allowed us to validate the presence of an intact Src homology 2 domain and STAT3 Tyr705 phosphorylation, which facilitate puncta formation and homodimerization...
February 5, 2018: Scientific Reports
Andy Jing Chen, Xiaojing Yuan, Junjie Li, Puting Dong, Iqbal Hamza, Ji-Xin Cheng
Heme, a hydrophobic and cytotoxic macrocycle, is an essential cofactor in a large number of proteins and is important for cell signaling. This must mean that heme is mobilized from its place of synthesis or entry into the cell to other parts of the cell where hemoproteins reside. However, the cellular dynamics of heme movement is not well understood, in large part due to the inability to image heme non-invasively in live biological systems. Here, using high-resolution transient absorption (TA) microscopy, we showed that heme storage and distribution is dynamic in C...
February 5, 2018: Analytical Chemistry
Karen A Conrad, Ronald Rodriguez, Eugenia C Salcedo, Jason M Rauceo
The ubiquitous presence of SPFH (Stomatin, Prohibitin, Flotillin, HflK/HflC) proteins in all domains of life suggests that their function would be conserved. However, SPFH functions are diverse with organism-specific attributes. SPFH proteins play critical roles in physiological processes such as mechanosensation and respiration. Here, we characterize the stomatin ORF19.7296/SLP3 in the opportunistic human pathogen Candida albicans. Consistent with the localization of stomatin proteins, a Slp3p-Yfp fusion protein formed visible puncta along the plasma membrane...
2018: PloS One
Sarah Villringer, Josef Madl, Taras Sych, Christina Manner, Anne Imberty, Winfried Römer
Cell adhesion is a crucial feature of all multicellular organisms, as it allows cells to organise themselves into tissues to carry out specific functions. Here, we present a mimetic approach that uses multivalent lectins with opposing binding sites to crosslink glycan-functionalised giant unilamellar vesicles. The crosslinking process drives the progression from contact puncta into elongated protocellular junctions, which form the vesicles into polygonal clusters resembling tissues. Due to their carbohydrate specificity, different lectins can be engaged in parallel with both natural and synthetic glycoconjugates to generate complex interfaces with distinct lectin domains...
January 31, 2018: Scientific Reports
Minsu Jang, Hyunju Kim, Rackhyun Park, Daum Jo, Eun-Ju Lee, Won Keun Oh, Junsoo Park
Autophagy regulation is important for tumor cell survival. Activation and inhibition of autophagy can sensitize tumor cells to anticancer drugs. However, few autophagy-regulating small molecules are available to increase the efficacy of anticancer drugs. Here, we report that 2,2'-methylenebis (6-tert-butyl 4-methylphenol), hereafter referred to as methylenebis, is a novel autophagy-regulating small molecule that sensitizes tumor cells to belotecan, which is a derivative of camptothecin, a topoisomerase I inhibitor...
December 29, 2017: Oncotarget
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