MicroRNAs (miRNAs) and Smad3, as key transcription factors in transforming growth factor-β1 (TGF-β1) signaling, help regulate various physiological and pathological processes. We investigated the roles of Smad3-regulated miRNAs with respect to lung adenocarcinoma cell apoptosis, proliferation, and metastasis. We observed that Smad3 and phospho-SMAD3 (p-Smad3) were decreased in miR-206- (or miR-140)-treated cells and there might be a feedback loop between miR-206 (or miR-140) and TGF-β1 expression. Smad3-related miRNAs affected tribbles homolog 2 (TRIB2) expression by regulating trib2 promoter activity through the CAGACA box. MiR-206 and miR-140 inhibited lung adenocarcinoma cell proliferation in vitro and in vivo by suppressing p-Smad3/Smad3 and TRIB2. Moreover, lung adenocarcinoma data supported a suppressive role for miR-206/miR-140 and an oncogenic role for TRIB2—patients with higher TRIB2 levels had poorer survival. In summary, miR-206 and miR-140, as tumor suppressors, induced lung adenocarcinoma cell death and inhibited cell proliferation by modifying oncogenic TRIB2 promoter activity through p-Smad3. MiR-206 and miR-140 also suppressed lung adenocarcinoma cell metastasis in vitro and in vivo by regulating EMT-related factors.
Cyclin D2 is involved in the pathology of vascular complications of type 2 diabetes mellitus (T2DM). This study investigated the role of cyclin‐D2‐regulated miRNAs in endothelial cell proliferation of T2DM. Results showed that higher glucose concentration (4.5 g/l) significantly promoted the proliferation of rat aortic endothelial cells (RAOECs), and significantly increased the expression of cyclin D2 and phosphorylation of retinoblastoma 1 (p‐RB1) in RAOECs compared with those under low glucose concentration. The cyclin D2‐3′ untranslated region is targeted by miR‐98, as demonstrated by miRNA analysis software. Western blot also confirmed that cyclin D2 and p‐RB1 expression was regulated by miR‐98. The results indicated that miR‐98 treatment can induce RAOEC apoptosis. The suppression of RAOEC growth by miR‐98 might be related to regulation of Bcl‐2, Bax and Caspase 9 expression. Furthermore, the expression levels of miR‐98 decreased in 4.5 g/l glucose‐treated cells compared with those treated by low glucose concentration. Similarly, the expression of miR‐98 significantly decreased in aortas of established streptozotocin (STZ)‐induced diabetic rat model compared with that in control rats; but cyclin D2 and p‐RB1 levels remarkably increased in aortas of STZ‐induced diabetic rats compared with those in healthy control rats. In conclusion, this study demonstrated that high glucose concentration induces cyclin D2 up‐regulation and miR‐98 down‐regulation in the RAOECs. By regulating cyclin D2, miR‐98 can inhibit human endothelial cell growth, thereby providing novel therapeutic targets for vascular complication of T2DM.
a b s t r a c tThe symplectic geometry method is introduced for exact bending solutions of moderately thick rectangular plates with two opposite edges simply supported. The basic equations for the plates are first transferred into Hamilton canonical equations. The whole state variables are then separated. Using the method of eigenfunction expansion in the symplectic geometry, typical examples for plates with selected boundary conditions are solved and exact bending solutions obtained. Since only the basic elasticity equations of the plates are used, this method eliminates the need to pre-determine the deformation function and is hence more reasonable than conventional methods. Numerical results were presented to demonstrate the validity and accuracy of this approach as compared to those reported in other literatures.Crown
Through
in situ transmission electron microscopy (TEM) observation,
we report the behaviors of phosphorus (P)-doped silicon nanowires
(SiNWs) during electrochemical lithiation/delithiation cycling. Upon
lithiation, lithium (Li) insertion causes volume expansion and formation
of the crystalline Li15Si4 phase in the P-doped
SiNWs. During delithiation, vacancies induced by Li extraction aggregate
gradually, leading to the generation of nanopores. The as-formed nanopores
can get annihilated with Li reinsertion during the following electrochemical
cycle. As demonstrated by our phase-field simulations, such first-time-observed
reversible nanopore formation can be attributed to the promoted lithiation/delithiation
rate by the P dopant in the SiNWs. Our phase-field simulations further
reveal that the delithiation-induced nanoporous structures can be
controlled by tuning the electrochemical reaction rate in the SiNWs.
The findings of this study shed light on the rational design of high-power
performance Si-based anodes.
Single nucleotide polymorphisms (SNPs) in human zinc ribbon domain containing 1 antisense RNA 1 (ZNRD1-AS1) have been associated with cancer development. In this meta-analysis, we more precisely estimated the associations between three expression quantitative trait loci SNPs in ZNRD1-AS1 (rs3757328, rs6940552, and rs9261204) and cancer susceptibility. The data for three SNPs were extracted from eligible studies, which included 5,293 patients and 5,440 controls. Overall, no significant associations between SNPs in ZNRD1-AS1 (rs3757328, rs6940552, and rs9261204) and cancer risk were observed. However, in further subgroup analyses based on cancer type, we found that the A allele of rs3757328 increased the risk of some cancer in both allele contrast (OR = 1.15, 95% CI = 1.05 – 1.25) and recessive models (OR = 1.79; 95% CI = 1.33 – 2.41). The A allele of rs6940552 and the G allele of rs9261204 also increased the risk of some cancer in an Asian population in allele contrast (OR = 1.17, 95% CI = 1.08 – 1.26, and OR = 1.25, 95% CI = 1.16 – 1.34, respectively) and recessive models (OR = 1.44, 95% CI = 1.18 – 1.77, and OR = 1.49; 95% CI = 1.23 – 1.80, respectively). Thus, rs3757328, rs6940552, and rs9261204 in ZNRD1-AS1 are all associated with increased some cancer risk in an Asian population.
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