Characterization of Side Populations in HNSCC: Highly Invasive, Chemoresistant and Abnormal Wnt Signaling

Side Population (SP) cells, a subset of Hoechst-low cells, are enriched with stem cells. Originally, SP cells were isolated from bone marrow but recently have been found in various solid tumors and cancer cell lines that are clonogenic in vitro and tumorigenic in vivo. In this study, SP cells from lymph node metastatic head and neck squamous cell carcinoma (HNSCC) cell lines were examined using flow cytometry and Hoechst 3342 efflux assay. We found that highly metastatic HNSCC cell lines M3a2 and M4e contained more SP cells compared to the low metastatic parental HNSCC cell line 686LN. SP cells in HNSCC were highly invasive in vitro and tumorigenic in vivo compared to non-SP cells. Furthermore, SP cells highly expressed ABCG2 and were chemoresistant to Bortezomib and etoposide. Importantly, we found that SP cells in HNSCC had abnormal activation of Wnt/β-catenin signaling as compared to non-SP cells. Together, these findings indicate that SP cells might be a major driving force of head and neck tumor formation and metastasis. The Wnt/β-catenin signaling pathway may be an important target for eliminating cancer stem cells in HNSCC

Preserving Private Knowledge In Decision Tree Learning

Abstract—Data mining over multiple data sources has become an important practical problem with applications in different areas. Although the data sources are willing to mine the union of their data, they don’t want to reveal any sensitive and private information to other sources due to competition or legal concerns. In this paper, we consider two scenarios where data are vertically or horizontally partitioned over more than two parties. We focus on the classification problem, and present novel privacy preserving decision tree learning methods. Theoretical analysis and experiment results show that these methods can provide good capability of privacy preserving, accuracy and efficiency

Augmented osteogenic responses in human aortic valve cells exposed to oxLDL and TLR4 agonist: a mechanistic role of Notch1 and NF-κB interaction.

Aortic valve calcification causes the progression of calcific aortic valve disease (CAVD). Stimulation of aortic valve interstitial cells (AVICs) with lipopolysaccharide (LPS) up-regulates the expression of osteogenic mediators, and NF-κB plays a central role in mediating AVIC osteogenic responses to Toll-like receptor 4 (TLR4) stimulation. Diseased aortic valves exhibit greater levels of oxidized low-density lipoprotein (oxLDL). This study tested the hypothesis that oxLDL augments the osteogenic responses in human AVICs through modulation of NF-κB and Notch1 activation. AVICs isolated from normal human aortic valves were treated with LPS (0.1 µg/ml), oxLDL (20 µg/ml) or LPS plus oxLDL for 48 h. OxLDL alone increased cellular bone morphogenetic protein-2 (BMP-2) levels while it had no effect on alkaline phosphatase (ALP) levels. Cells exposed to LPS plus oxLDL produced higher levels of BMP-2 and ALP than cells exposed to LPS alone. Further, LPS plus oxLDL induced greater NF-κB activation, and inhibition of NF-κB markedly reduced the expression of BMP-2 and ALP in cells treated with LPS plus oxLDL. OxLDL also induced Notch1 activation and resulted in augmented Notch1 activation when it was combined with LPS. Inhibition of Notch1 cleavage attenuated NF-κB activation induced by LPS plus oxLDL, and inhibition of NF-κB suppressed the expression of BMP-2 and ALP induced by the synergistic effect of Jagged1 and LPS. These findings demonstrate that oxLDL up-regulates BMP-2 expression in human AVICs and synergizes with LPS to elicit augmented AVIC osteogenic responses. OxLDL exerts its effect through modulation of the Notch1-NF-κB signaling cascade. Thus, oxLDL may play a role in the mechanism underlying CAVD progression

IL-37 Suppresses MyD88-mediated Inflammatory Responses in Human Aortic Valve Interstitial Cells

Abstract Calcific aortic valve disease (CAVD) is common among the elderly, and aortic valve interstitial cells (AVICs) exhibit unique inflammatory and osteogenic responses to proinflammatory stimulation, which plays an important role in valvular fibrosis and calcification. Thus, suppression of AVIC proinflammatory response may have therapeutic utility for the prevention of CAVD progression. Interleukin (IL)-37, an antiinflammatory cytokine, reduces tissue inflammation. This study aimed to test the hypothesis that IL-37 suppresses human AVIC inflammatory responses to Toll-like receptor (TLR) agonists. Human AVICs were exposed to Pam3CSK4, poly(I:C) and lipopolysaccharide in the presence and absence of recombinant human IL-37. Stimulation of TLR4 increased the production of intercellular adhesion molecule-1, IL-6, IL-8 and monocyte chemoattractant protein-1. Knockdown of myeloid differentiation factor 88 (MyD88) or TIR-domain-containing adaptor-inducing interferon-β differentially affected inflammatory mediator production following TLR4 stimulation. IL-37 reduced production of these inflammatory mediators induced by TLR4. Moreover, knockdown of IL-37 enhanced induction of these mediators by TLR4. IL-37 also suppressed inflammatory mediator production induced by the MyD88-dependent TLR2, but had no effect on the inflammatory responses to the TRIF-dependent TLR3. Furthermore, IL-37 inhibited NF-κB activation induced by TLR2 or TLR4 through a mechanism dependent of IL-18 receptor α-chain. Activation of TLR2, TLR3 or TLR4 upregulates the production of inflammatory mediators in human AVICs. IL-37 suppresses MyD88-mediated responses to reduce inflammatory mediator production following stimulation of TLR2 and TLR4. This antiinflammatory cytokine may be useful for suppression of aortic valve inflammation elicited by MyD88-dependent TLR signaling

Characterization of the Auxin Efflux Transporter PIN Proteins in Pear

PIN-FORMED (PIN) encodes a key auxin polar transport family that plays a crucial role in the outward transport of auxin and several growth and development processes, including dwarfing trees. We identified a dwarfing pear rootstock ‘OHF51’ (Pyrus communis), which limits the growth vigor of the ‘Xueqing’ (Pyrus bretschneideri × Pyrus pyrifolia) scion, and isolated 14 putative PbPINs from the pear Pyrus bretschneideri. The phylogenic relationships, structure, promoter regions, and expression patterns were analyzed. PbPINs were classified into two main groups based on the protein domain structure and categorized into three major groups using the neighbor-joining algorithm. Promoter analysis demonstrated that PbPINs might be closely related to plant growth and development. Through quantitative real-time PCR (qRT-PCR) analysis, we found that the expression patterns of 14 PbPINs varied upon exposure to different organs in dwarfing and vigorous stocks, ‘OHF51’ and ‘QN101’ (Pyrus betulifolia), indicating that they might play varying roles in different tissues and participated in the regulation of growth vigor. These results provide fundamental insights into the characteristics and evolution of the PINs family, as well as the possible relationship between dwarfing ability and auxin polar transport

LINC00891 regulated by miR-128-3p/GATA2 axis impedes lung cancer cell proliferation, invasion and EMT by inhibiting RhoA pathway

Long non-coding RNA (lncRNA) LINC00891 knockdown is associated with poor prognosis of lung adenocarcinoma, but the underlying mechanism remains to be further explored. Here, we found that LINC00891 expression is downregulated in lung cancer tissues and cell lines compared with that in adjacent normal tissues and normal lung epithelial cells. LINC00891 overexpression impedes cell proliferation, invasion, migration and epithelial-to-mesenchymal transition (EMT) process in lung cancer cells. Mechanistic research showed that GATA2 directly binds to LINC00891 promoter and transcriptionally regulates LINC00891 expression. Meanwhile, GATA2 was identified as a target of miR-128-3p, and it is negatively regulated by miR-128-3p. Moreover, overexpression of GATA2 suppresses lung cancer cell proliferation, invasion, migration, and EMT process. Furthermore, LINC00891 restrains the RhoA pathway activity, and treatment with CCG-1423 (a specific RhoA pathway inhibitor) antagonizes the promoting effect of LINC00891 knockdown on cell malignant behaviors. Additionally, silencing of LINC00891 promotes xenograft tumor growth, which can be reversed by administration with CCG-1423. In summary, LINC00891 regulated by the miR-128-3p/GATA2 axis restrains lung cancer cell malignant progression and hinders xenograft tumor growth by suppressing the RhoA pathway