Analysis and Verification of Heat Dissipation Structures Embedded in Substrates in Power Chips Based on Square Frustums Thermal through Silicon Vias.

A novel heat dissipation structure composed of square frustums thermal through silicon via array and embedded in P-type (100) silicon substrate is proposed to improve the heat dissipation capacity of power chips while reducing process difficulty. Based on theoretical analysis, the heat transfer model and thermo-electric coupling reliability model of a power chip with the proposed heat dissipation structure are established. A comparative study of simulation indicates that the proposed heat dissipation structure, which can avoid problems such as softness, poor rigidity, fragility and easy fracture caused by thinning chips has better heat dissipation capability than thinning the substrate of power chips.

Integrative analysis of single-cell and bulk RNA-sequencing data revealed T cell marker genes based molecular sub-types and a prognostic signature in lung adenocarcinoma.

Immunotherapy has emerged as a promising modality for addressing advanced or conventionally drug-resistant malignancies. When it comes to lung adenocarcinoma (LUAD), T cells have demonstrated significant influence on both antitumor activity and the tumor microenvironment. However, their specific contributions remain largely unexplored. This investigation aimed to delineate molecular subtypes and prognostic indicators founded on T cell marker genes, thereby shedding light on the significance of T cells in LUAD prognosis and precision treatment. The cellular phenotypes were identified by scrutinizing the single-cell data obtained from the GEO repository. Subsequently, T cell marker genes derived from single-cell sequencing analyses were integrated with differentially expressed genes from the TCGA repository to pinpoint T cell-associated genes. Utilizing Cox analysis, molecular subtypes and prognostic signatures were established and subsequently verified using the GEO dataset. The ensuing molecular and immunological distinctions, along with therapy sensitivity between the two sub-cohorts, were examined via the ESTIMATE, CIBERSORT, and ssGSEA methodologies. Compartmentalization, somatic mutation, nomogram development, chemotherapy sensitivity prediction, and potential drug prediction analyses were also conducted according to the risk signature. Additionally, real-time qPCR and the HPA database corroborated the mRNA and protein expression patterns of signature genes in LUAD tissues. In summary, this research yielded an innovative T cell marker gene-based signature with remarkable potential to prognosis and anticipate immunotherapeutic outcomes in LUAD patients.

Photon-Energy-Dependent Reversible Charge Transfer Dynamics of Double Perovskite Nanocrystal-Polymer Nanocomposites.

Combining steady-state photoluminescence and transient absorption (TA) spectroscopy, we have investigated the photoinduced charge transfer dynamics between lead-free Mn-doped Cs2NaIn0.75Bi0.25Cl6 double perovskite (DP) nanocrystals (NCs) and conjugated poly[2-methoxy-5-(3',7'-dimethyloctyloxy)-1,4-phenylenevinylene] (MDMO-PPV). Upon ultraviolet-A excitation, the photoinduced absorption feature of DP NCs/MDMO-PPV nanocomposites disappeared, and the stimulated emission weakened in the TA spectrum. This was due to charge transfer from the MDMO-PPV polymers to DP NCs. Upon a higher photon-energy ultraviolet-C excitation, stimulated emission and photoinduced absorption features vanished, indicating there existed a reversible charge transfer from DP NCs to MDMO-PPV polymers. Reversible charge transfer of Mn-doped DP NCs/MDMO-PPV nanocomposites was tuned by varying the excitation photon-energy. The manipulation of reversible charge transfer dynamics in the perovskite-polymer nanocomposites opens a new avenue for optical and optoelectronic applications.

Aptamer-siRNA chimera and gold nanoparticle modified collagen membrane for the treatment of malignant pleural effusion.

Malignant pleural effusion is one of the most common complications of advanced lung cancer and there is no effective clinical treatment at present. Here, we constructed an aptamer-siRNA chimeras/PEI/PEG/gold nanoparticle (AuNP)/collagen membrane that can progressively activate T cells by layer by layer assembly. Electron microscope showed this collagen membrane could be divided into 10 layers with a total thickness of 50-80µm, and AuNPs could be observed. Aptamer-siRNA chimeras could bind specifically to OX40+ cells and silencing programmed death receptor-1 (PD-1) gene. In vitro experiments demonstrated that chimeras/PEI/PEG/AuNPs gradually activated T cells to continuously kill lung adenocarcinoma cells in malignant pleural effusion. Animal experiments showed that chimeras/PEI/PEG/AuNP/collagen membrane effectively treated malignant pleural effusion. Compared with PD-1 inhibitor group, the number of cancer cells, ki-67 proliferation index and CD44 expression in the pleural effusion was significantly decreased and the lymphocyte/cancer cell ratio was significantly increased in the chimeras/AuNP-CM group. Flow cytometry showed that compared with PD-1 inhibitor group, T cell number in the chimeras/AuNP-CM group was significantly increased, while the proportion of PD-1+ T cells was markedly decreased. In conclusion, we constructed an chimeras/PEI/PEG/AuNP/collagen membrane, which was more effective in the treatment of malignant pleural effusion, and had less side effects than PD-1 inhibitors.

The Inhibitory Effect of Regulatory T Cells on the Intimal Hyperplasia of Tissue-Engineered Blood Vessels in Diabetic Pigs.

Severe inflammatory response and functional impairment of endothelial progenitor cells (EPCs) often lead to the implantation failure of EPC-captured tissue-engineered blood vessels (TEBVs) in diabetes. Regulatory T cells (Treg cells) are the most important inhibitory immune cells, but their effects in angiogenesis remain undefined, and the differences in the microenvironment may be an important reason. Here, we constructed a TEBV coated with an anti-CD34 antibody-functionalized heparin-collagen multilayer (anti-CD34 antibody-modified TEBV) using layer-by-layer self-assembly. Then, TEBVs were implanted into diabetic pigs. All TEBVs remained unobstructed 60 days after implantation, although varying degrees of intimal hyperplasia were detectable. Severe intimal hyperplasia was observed in the control group and peripheral injection of Treg cells group. Intravenous injection of Treg cells significantly inhibited intimal hyperplasia, inflammation, and cell apoptosis. Moreover, intravenous injection increased the proportion of circulating EPCs, while peripheral injection did not have these effects and reduced microvessel density around the TEBV. Interestingly, many Nestin+ cells could be detected in TEBVs, most of which were fusiform, showing the characteristics of smooth-muscle cells. Treg cell intravenous transplantation markedly reduced the number of Nestin+ cells in the TEBV. In conclusion, Treg cells inhibited the intimal hyperplasia of TEBVs in diabetic pigs by promoting EPC mobilization, anti-inflammatory action, and cellular protection.

MiR-192/NKRF axis confers lung cancer cell chemoresistance to cisplatin via the NF-κB pathway.

BACKGROUND: Chemoresistance influences the therapeutic effect of cisplatin and remains a major obstacle to its clinical use. MicroRNAs are associated with drug resistance of various tumors. However, the association between microRNAs and cisplatin in lung cancer remains largely unclear. METHODS: MicroRNA expression profile was identified by microRNA microarray between the lung cancer cisplatin-sensitive cell line A549 (A549) and cisplatin-resistant cell line A549/DDP (A549/DDP) and confirmed by quantitative real-time-PCR (qRT-PCR). In vitro loss- and gain-of-function studies were performed to reveal the biological function of miR-192 and related mechanism of the microRNA-192/NKRF axis in lung cancer cell cisplatin resistance. RESULTS: Increased miR-192 expression was detected in A549/DDP cells compared to A549. High miR-192 expression significantly suppressed apoptosis, enhanced proliferation, and conferred resistance to cisplatin in lung cancer cells. NF-κB repressing factor (NKRF), which is involved in the regulation of the NF-κB signaling pathway, was identified as a direct target of miR-192. Overexpression of miR-192 significantly increased the nuclear protein amount and transcriptional activation of NF-κB and expression of cIAP1, cIAP2, Bcl-xl and XIAP, whereas decreased miR-192 expression did the opposite. Inhibition of the NF-κB signal pathway by curcumin reversed the effect of upregulation of miR-192 on proliferation, apoptosis and cisplatin-resistance in lung cancer cells. These results indicated that miR-192/ NKRF axis enhances the cisplatin resistance of lung cancer cells through activating the NF-κB pathway in vitro. CONCLUSIONS: MiR-192 plays a crucial role in cisplatin-resistance of lung cancer cells. Thus, MiR-192 may represent a therapeutic target for overcoming resistance to cisplatin-based chemotherapy in lung cancer.

MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer.

BACKGROUND: MicroRNAs (miRNAs) have been reported to play significant roles in non-small-cell lung cancer (NSCLC). However, the roles of microRNA (miR)-1915-3p in NSCLC remain unclear. In this study, we aimed to explore the biological functions of miR-1915-3p in NSCLC. METHODS: The expression of miR-1915-3p and SET nuclear proto-oncogene (SET) in NSCLC tissues were examined by quantitative real-time PCR (qRT-PCR). Migratory and invasive abilities of lung cancer were tested by wound healing and transwell invasion assay. The direct target genes of miR-1915-3p were measured by dual-luciferase reporter assay and western blot. Finally, the regulation between METTL3/YTHDF2/KLF4 axis and miR-1915-3p were evaluated by qRT-PCR, promoter reporter assay and chromatin immunoprecipitation (CHIP). RESULTS: miR-1915-3p was downregulated in NSCLC tissues and cell lines, and inversely associated with clinical TNM stage and overall survival. Functional assays showed that miR-1915-3p significantly suppressed migration, invasion and epithelial-mesenchymal transition (EMT) in NSCLC cells. Furthermore, miR-1915-3p directly bound to the 3'untranslated region (3'UTR) of SET and modulated the expression of SET. SET inhibition could recapitulate the inhibitory effects on cell migration, invasion and EMT of miR-1915-3p, and restoration of SET expression could abrogate these effects induced by miR-1915-3p through JNK/Jun and NF-κB signaling pathways. What's more, miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. CONCLUSIONS: These findings demonstrate that miR-1915-3p function as a tumor suppressor by targeting SET and may have an anti-metastatic therapeutic potential for lung cancer treatment.

Prognostic and immunological significance of metastasis associated lung adenocarcinoma transcript 1 among different kinds of cancers.

LncRNAs belong to the type of noncoding RNA transcripts, which exceed 200 nucleotides in size. MALAT1 as one of the earlier identified lncRNAs in cancer is investigated by more and more scientific researchers. Expression, clinical significance and function of MALAT1 in pan-cancer exist as big difference. To detect the expression and clinical significance of MALAT1 gene precisely and comprehensively among different kinds of cancers, some classical databases such as GEPIA, TIMER, KM Plotter, and PrognoScan were fully applied. An immunological role of MALAT1 among different kinds of cancers was also determined in TIMER database. Our results showed that MALAT1 was differently expressed in different kinds of cancers using GEPIA, Oncomine, and TIMER databases to analyze. Especially, MALAT1 high RNA level was related to the early stage in lung and gastric cancer patients. MALAT1 expression was closely related to prognosis among different cancer patients. Furthermore, expression of MALAT1 was related to tumor immune cell infiltrating. Expression level of MALAT1 was also related to immune makers such as macrophage, T cell, NK cells, and so on. These findings indicate that MALAT1 could be a potential prognostic biomarker of some kinds of cancer and was significantly correlated with tumor-infiltrating immune cells in a wide variety of cancers.

Exosome-based targeted RNA delivery for immune tolerance induction in skin transplantation.

Exosomes have been widely applied to the delivery of RNA and small molecules currently. However, the low targeting and specificity greatly limited the effect of exosome delivery. Here we designed an exosome that can perform the targeted delivery of two different types of RNA. Based on the mesenchymal stem cells (MSCs) derived exosomes, the RNA delivery system of targeted dendritic cells (DC-Exosome) was constructed, using the layer by layer self-assembly. DC-Exosomes can specifically bind to DCs, while guiding the endocytosis of chimeras and exosome. Then aptamer/siRNA chimera was cut into mTOR siRNA by Dicer, and microRNA was released from exosome under lysosomal digestion. SIGN aptamer performed the rapid induction of immune tolerance, and later mTOR siRNA was formed to inhibit mTOR pathway and suppress immune responses. Exosomes could maintain long time-stability after PEG-PEI polyplexes modification and promote HLA-G expression in DCs continuously. Animal experiments showed that DC-Exosomes could induce immune tolerance at 3, 7, and 14 days after skin transplantation. Compared with the microRNA-Exosome group, the number of CD11c+ DCs in DC-Exosome group decreased, while the proportion of HLA-G+ DCs increased remarkably. In conclusion, we constructed a new exosome-based targeted delivery system which could effectively induce the immune tolerance in transplantation.

Recent BCR stimulation induces a negative autoregulatory loop via FBXO10 mediated degradation of HGAL.

Regulating B-cell receptor (BCR) signaling after antigenic stimulation is essential to properly control immune responses. Currently known mechanisms of inhibiting BCR signaling are via co-receptor stimulation and downstream immunoreceptor tyrosine-based inhibition motif (ITIM) phosphorylation. Herein we demonstrate that BCR stimulation induces rapid and reversible palmitoylation of the SCF-FBXO10 ubiquitin E3 ligase. This results in FBXO10 relocation to the cell membrane, where it targets the human germinal center-associated lymphoma (HGAL) protein for ubiquitylation and degradation, leading to decreases in both BCR-induced calcium influx and phosphorylation of proximal BCR effectors. Importantly, FBXO10 recognition and degradation of HGAL is phosphorylation independent and instead relies on a single evolutionarily conserved HGAL amino acid residue (H91) and FBXO10 relocalization to the cytoplasmic membrane. Together our findings demonstrate the first evidence of negative BCR signaling regulation from direct BCR stimulation and define the temporospatial functions of the FBXO10-HGAL axis. FBXO10 is infrequently mutated in DLBCL but some of these mutations deregulate BCR signaling. These observations may have important implications on lymphomagenesis and other immune processes.

Knockdown of long non-coding RNA linc-ITGB1 inhibits cancer stemness and epithelial-mesenchymal transition by reducing the expression of Snail in non-small cell lung cancer.

BACKGROUND: The main cause of death in patients with non-small cell lung cancer (NSCLC) is the progression of cancer metastasis, which can be attributed to multiple factors, such as cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) play important roles in the regulation of the cell cycle, cell proliferation, immune responses, and metastasis in cancers, but the potential roles and mechanisms of lincRNAs in CSC-like properties of cancer have not yet been elucidated. METHODS: Human NSCLC cell lines (A549 and H1299), highly metastatic cell lines (L9981 and 95D), and their corresponding low-metastatic cell lines (NL9980 and 95C) were subject to quantitative real-time PCR and Western blot, transwell invasion, colony formation, and wound healing assays. RESULTS: Linc-ITGB1 was greatly upregulated in CSC spheres. Linc-ITGB1 knockdown markedly inhibited CSC formation and the expression of stemness-associated genes, such as Sox2, Nanog, Oct-4, c-Myc, and CD133. Depletion of linc-ITGB1 expression also inhibited the in vitro invasive and migratory potential of cells, and further analysis indicated that linc-ITGB1 knockdown increased the expression of the epithelial marker E-cadherin and downregulated the mesenchymal markers vimentin and fibronectin. The EMT-related transcription factor Snail mediated these effects of linc-ITGB1 in NSCLC, and overexpression of Snail significantly reversed the inhibitory effects of linc-ITGB1 depletion. CONCLUSION: Overall, our study demonstrated that linc-ITGB1 promoted NSCLC cell EMT and cancer stemness by regulating Snail expression.

Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy.

The forkhead/winged helix transcription factor (Fox) p3 can regulate the expression of various genes, and it has been reported that the transfer of Foxp3-positive T cells could ameliorate cardiac hypertrophy and fibrosis. Triptolide (TP) can elevate the expression of Foxp3, but its effects on cardiac hypertrophy remain unclear. In the present study, neonatal rat ventricular myocytes (NRVM) were isolated and stimulated with angiotensin II (1 µmol/L) to induce hypertrophic response. The expression of Foxp3 in NRVM was observed by using immunofluorescence assay. Fifty mice were randomly divided into five groups and received vehicle (control), isoproterenol (Iso, 5 mg/kg, s.c.), one of three doses of TP (10, 30, or 90 µg/kg, i.p.) for 14 days, respectively. The pathological morphology changes were observed after Hematoxylin and eosin, lectin and Masson's trichrome staining. The levels of serum brain natriuretic peptide (BNP) and troponin I were determined by enzyme-linked immunosorbent assay and chemiluminescence, respectively. The mRNA and protein expressions of α- myosin heavy chain (MHC), ß-MHC and Foxp3 were determined using real-time PCR and immunohistochemistry, respectively. It was shown that TP (1, 3, 10 µg/L) treatment significantly decreased cell size, mRNA and protein expression of ß-MHC, and upregulated Foxp3 expression in NRVM. TP also decreased heart weight index, left ventricular weight index and, improved myocardial injury and fibrosis; and decreased the cross-scetional area of the myocardium, serum cardiac troponin and BNP. Additionally, TP markedly reduced the mRNA and protein expression of myocardial ß-MHC and elevated the mRNA and protein expression of α-MHC and Foxp3 in a dose-dependent manner. In conclusion, TP can effectively ameliorate myocardial damage and inhibit cardiac hypertrophy, which is at least partly related to the elevation of Foxp3 expression in cardiomyocytes.

Protection of Pentoxifylline against Testis Injury Induced by Intermittent Hypobaric Hypoxia.

To investigate the effect of pentoxifylline (PTX) on spermatogenesis dysfunction induced by intermittent hypobaric hypoxia (IHH) and unveil the underlying mechanism, experimental animals were assigned to Control, IHH+Vehicle, and IHH+PTX groups and exposed to 4 cycles of 96 h of hypobaric hypoxia followed by 96 h of normobaric normoxia for 32 days. PTX was administered for 32 days. Blood and tissue samples were collected 7 days thereafter. Serum malondialdehyde levels were used to assess lipid peroxidation; ferric-reducing antioxidant power (FRAP), superoxide dismutase, and catalase and glutathione peroxidase enzyme activities were assessed to determine antioxidant capacity in various samples. Testis histopathology was assessed after hematoxylin-eosin staining by Johnsen's testicular scoring system. Meanwhile, testosterone synthase and vimentin amounts were assessed by immunohistochemistry. Sperm count, motility, and density were assessed to determine epididymal sperm quality. IHH treatment induced significant pathological changes in testicular tissue and enhanced serum lipid peroxide levels, while reducing serum FRAP, antioxidant enzyme activities, and testosterone synthase expression. Moreover, IHH impaired epididymal sperm quality and vimentin structure in Sertoli cells. Oral administration of PTX improved the pathological changes in the testis. IHH may impair spermatogenesis function of testicular tissues by inducing oxidative stress, but this impairment could be attenuated by administration of PTX.

Regulation of MALAT1 expression by TDP43 controls the migration and invasion of non-small cell lung cancer cells in vitro.

MALAT1 is a non-coding RNA overexpressed in non-small cell lung cancer (NSCLC). TDP-43 is a ubiquitously expressed, MALAT1-binding protein implicated in cancer development. We hypothesized that MALAT1 expression level is regulated in lung cancer by TDP-43. We analyzed their functions in cultured NSCLC cells. Downregulation of MALAT1 or TDP-43 expression by siRNA not only markedly suppressed NSCLC cell growth, as measured by the MTT assay in vitro cultured NSCLC cells (P < 0.05), but also noticeably impaired the migration and invasion of NSCLC cells, as analyzed by the migration and invasion assay. We also confirm that TDP-43 directly bound to MALAT1 RNA by a RNA immunoprecipitation (RIP) assay and by luciferase reporter activity assay. In a RT-PCR assay, silencing TDP-43 expression effectively decreased MALAT1 RNA transcript level. In contrast, TDP-43 overexpression markedly increased MALAT1 transcript level. In summary, these findings demonstrated that MALAT1 expression by regulation of TDP-43 controls cellular growth, migration, and invasion of NSCLCs.

Expression and clinical significance of the microRNA-200 family in gastric cancer.

Gastric cancer is one of the most common malignant tumors and one of the leading causes of cancer-related mortality. Recent studies have revealed that there is a difference in microRNA (miR/miRNA) profiles between cancerous and normal tissues. To find a potentially useful prognostic predictor and a promising therapeutic tool for gastric cancer, the present study investigated the expression and clinical significance of the miR-200 family in gastric cancer. The miR-200 family has five members: hsa-miR-200a, hsa-miR-200b, hsa-miR-200c, hsa-miR-141 and hsa-miR-429. In 46 clinical samples of gastric cancer and paired non-cancerous tissues, the present study observed that the expression levels of the miR-200 family in the cancer tissues were significantly lower than those in the non-cancerous tissues (P<0.001). Lower levels of the five family members were associated with histological grade and the presence of an intravascular cancer embolus (P<0.05). The results revealed that the miR-200 family is downregulated in gastric cancer, and that there are significant differences in the expression of the miR-200 family between normal and cancer tissues. The miR-200 family may therefore become a potentially useful prognostic predictor of the aggressiveness of gastric cancer and a possible therapeutic tool in affected patients.

Expression of MALAT1 in the peripheral whole blood of patients with lung cancer.

A blood-based biomarker assay is a non-invasive way to screen that can identify lung cancer at an earlier stage to improve the clinical outcome. MALAT1 is a broadly expressed, long non-coding RNA in human tissues and is overexpressed in numerous human carcinomas. The potential of MALAT1 in the whole blood of lung cancer was evaluated. In the present study, blood samples of patients with lung cancer and healthy volunteers (controls) were recruited and analyzed by quantitative polymerase chain reaction (qPCR) for MALAT1 expression and clinicopathological data. Lung cancer tissues were also analyzed by qPCR. The expression of MALAT1 in the whole blood of lung cancer was lower compared to the control. The area under the receiver operator curve was 0.718 (P<0.001). Relatively, the expression of MALAT1 was stronger in the whole blood of lung cancer with metastasis compared to non-metastasis. Additionally, the whole blood with bone or brain metastasis exhibited a higher expression of MALAT1 compared to the blood with lymph node or pleura metastasis. Subsequently, a lower expression of MALAT1 was detected in metastatic lymph node tissues than that of the carcinoma in situ of the lung. Taken together, these results indicate that MALAT1 as a biomarker to screen lung cancer may represent a host response to lung cancer.

MALAT1 is an oncogenic long non-coding RNA associated with tumor invasion in non-small cell lung cancer regulated by DNA methylation.

MALAT1 is an important long noncoding RNA in tumor progression. Here we showed that the expression of MALAT1 was upregulated in non-small cell lung cancer cells (NSCLCs) or tissues as compared with the normal lung cell or tissues. Thus, the knockdown of MALAT1 led to decreased cell migration and invasion. Next we also found that CXCL5 as a downstream gene of MALAT1 regulated cell migration and invasion. However the regulation of MALAT1 expression was rarely known. Here we found that the treatment with SAM suppressed of MALAT1 expression. Finally, we showed that the methylated forms of MALAT1 promoter in lung cancer cells or tissues decreased compared with normal lung cells or tissues. These demonstrated that the expression of MALAT1 was dependent on the methylation. Overall, our findings illuminate the oncogenic function of MALAT1 which is regulated by DNA methylation that might provide potential clinical application in NSCLC.

Fast-track surgery for gastroenteric neoplasms: a meta-analysis.

AIMS AND BACKGROUND: Fast-track surgery has been shown to enhance postoperative recovery. The objective of the study was to determine the differences of fast-track surgery and conventional care for patients with gastroenteric neoplasms. METHODS AND STUDY DESIGN: We searched PubMed, EMBASE, and the Cochrane Library for related trials to compare hospital stay and rates of complications and readmission. RESULTS: Thirteen randomized controlled trials, with 1,962 patients, were included. Results showed the length of hospital stay was significantly reduced in the fast-track group. The complications rate was lowered in colorectal surgery. There were no significant differences in rate of readmissions. CONCLUSIONS: Current trials show that fast-track surgery may reduce the length of hospital stay and lower the rate of complications of gastroenteric surgery.

MicroRNA-200c regulates the sensitivity of chemotherapy of gastric cancer SGC7901/DDP cells by directly targeting RhoE.

Gastric cancer remains a worldwide burden as the second leading cause of cancer-related death. Drug resistance of chemotherapy looms as a major clinical obstacle to successful treatment. Recent evidence indicated that miRNA-200c can restore the sensitivity of NSCLC cells to cisplatin and cetuximab. The expression of miRNA-200c and RhoE were investigated in gastric cancer tissues and cells (SGC7901 and SGC7901/DDP) by qRT-PCR. A luciferase reporter assay was done to understand the potential correlation between miRNA-200c and RhoE. Pre-miR-200c was transfected in SGC7901/DDP cells to confirm whether miRNA-200c could regulate RhoE expression. RhoE was knocked down to explore the role of RhoE on sensitivity of chemotherapy in gastric cancer by MTT. Western blot analysis was performed to further explore the mechanism of RhoE in regulating drug resistance. The results showed that miRNA-200c was significantly lower in cancerous tissues than those in the paired normal tissues, whereas the expression of RhoE was just the opposite. The significant difference of miRNA-200c and RhoE were observed between SGC7901 cells and SGC7901/DDP cells. miRNA-200c has target sites in the 3'-UTR of RhoE mRNA by luciferase reporter assay. Transfection of pre-miR-200c reduces RhoE expression. Meanwhile, the knockdown of RhoE enhanced the sensitivity of SGC7901/DDP cells and changed expression of some genes. These suggested that miRNA-200c regulated the sensitivity of chemotherapy to cisplatin (DDP) in gastric cancer by possibly targeting RhoE.

Stanniocalcin1 (STC1) Inhibits Cell Proliferation and Invasion of Cervical Cancer Cells.

STC1 is a glycoprotein hormone involved in calcium/phosphate (Pi) homeostasis. There is mounting evidence that STC1 is tightly associated with the development of cancer. But the function of STC1 in cancer is not fully understood. Here, we found that STC1 is down-regulated in Clinical tissues of cervical cancer compared to the adjacent normal cervical tissues (15 cases). Subsequently, the expression of STC1 was knocked down by RNA interference in cervical cancer CaSki cells and the low expression promoted cell growth, migration and invasion. We also found that STC1 overexpression inhibited cell proliferation and invasion of cervical cancer cells. Moreover, STC1 overexpression sensitized CaSki cells to drugs. Further, we showed that NF-κB p65 protein directly bound to STC1 promoter and activated the expression of STC1 in cervical cancer cells. Thus, these results provided evidence that STC1 inhibited cell proliferation and invasion through NF-κB p65 activation in cervical cancer.