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Kinesin family member C1 (KIFC1) is a kinesin-14 motor protein, and its abnormal upregulation promotes the malignant behavior of cancer cells. N6-methyladenosine (m6A) RNA methylation is a common modification of eukaryotic messenger RNA and affects RNA expression. In this study, we explored how KIFC1 regulated head and neck squamous cell carcinoma (HNSCC) tumorigenesis and how m6A modification affected KIFC1 expression. A bioinformatics analysis was performed to screen for genes of interest, and in vitro and in vivo studies were carried out to investigate the function and mechanism of KIFC1 in HNSCC tissues. We observed that the expression of KIFC1 in HNSCC tissues was significantly higher than that in normal or adjacent normal tissues. Patients with cancer with higher KIFC1 expression have a lower tumor differentiation status. Demethylase alkB homolog 5, a cancer-promoting factor in HNSCC tissues, could interact with KIFC1 messenger RNA and posttranscriptionally activate KIFC1 through m6A modification. KIFC1 downregulation suppressed HNSCC cell growth and metastasis in vivo and in vitro. However, overexpression of KIFC1 promoted these malignant behaviors. We demonstrated that KIFC1 overexpression activated the oncogenic Wnt/ß-catenin pathway. KIFC1 interacted with the small GTPase Ras-related C3 botulinum toxin substrate 1 (Rac1) at the protein level and increased its activity. The Rho GTPase Rac1 was indicated to be an upstream activator of the Wnt/ß-catenin signaling pathway, and its Rac1 inhibitor, NSC-23766, treatment reversed the effects caused by KIFC1 overexpression. Those observations demonstrate that abnormal expression of KIFC1 may be regulated by demethylase alkB homolog 5 in an m6A-dependent manner and promote HNSCC progression via the Rac1/Wnt/ß-catenin pathway.
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Neoplasias de Cabeça e Pescoço , Via de Sinalização Wnt , Humanos , Enzimas AlkB/genética , Enzimas AlkB/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Família , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Cinesinas/genética , Cinesinas/metabolismo , RNA , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Via de Sinalização Wnt/genéticaRESUMO
Far-field super-resolution optical microscopies have achieved incredible success in life science for visualization of vital nanostructures organized in single cells. However, such resolution power has been much less extended to material science for inspection of human-made ultrafine nanostructures, simply because the current super-resolution optical microscopies modalities are rarely applicable to nonfluorescent samples or unlabeled systems. Here, we report an antiphase demodulation pump-probe (DPP) super-resolution microscope for direct optical inspection of integrated circuits (ICs) with a lateral resolution down to 60 nm. Because of the strong pump-probe (PP) signal from copper, we performed label-free super-resolution imaging of multilayered copper interconnects on a small central processing unit (CPU) chip. The label-free super-resolution DPP optical microscopy opens possibilities for easy, fast, and large-scale electronic inspection in the whole pipeline chain for designing and manufacturing ICs.
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Microscopia , Nanoestruturas , HumanosRESUMO
Long non-coding RNAs (lncRNAs), which are longer than 200 nt, have been proved to play a role in promoting or inhibiting cancer progression. The following study investigated the role and underlying mechanisms of lncRNA RP11-159K7.2 in laryngeal squamous cell carcinoma (LSCC) progression. Briefly, in situ hybridization (ISH) and real-time quantitative PCR (RT-qPCR) showed higher expression of RP11-159K7.2 in LSCC tissues and cell lines. Patients with low expression level of RP11-159K7.2 lived longer compared to those with high expression of RP11-159K7.2 (χ2 = 39.111, ***P < 0.001). Multivariate Cox regression analysis suggested that lncRNA RP11-159K7.2 was an independent prognostic factor for LSCC patients (HR = 2.961, ***P < 0.001). Furthermore, to investigate the potential involvement of RP11-159K7.2 in the development of LSCC, we knocked out the expression of endogenous RP11-159K7.2 in TU-212 cells and AMC-HN-8 cells via CRISPR/Cas9 double vector lentiviral system. RP11-159K7.2 knockout decreased LSCC cell growth and invasion both in vitro and in vivo. Mechanically, we found that RP11-159K7.2 could positively regulate the expression of DNMT3A by sponging miR-206. In addition, a feedback loop was also discovered between DNMT3A and miR-206. To sum up, these findings suggest that lncRNA RP11-159K7.2 could be used as a potential biomarker for prognosis and treatment of LSCC.
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Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , DNA (Citosina-5-)-Metiltransferases/metabolismo , Progressão da Doença , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Sequência de Bases , Sistemas CRISPR-Cas/genética , Linhagem Celular Tumoral , Proliferação de Células , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA/genética , DNA Metiltransferase 3A , Retroalimentação Fisiológica , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Prognóstico , RNA Longo não Codificante/genética , Regulação para Cima/genéticaRESUMO
An AI-empowered indoor digital contact-tracing system was developed using a centralized architecture and advanced low-energy Bluetooth technologies for indoor positioning, with careful preservation of privacy and data security. We analyzed the contact pattern data from two RCHs and investigated a COVID-19 outbreak in one study site. To evaluate the effectiveness of the system in containing outbreaks with minimal contacts under quarantine, a simulation study was conducted to compare the impact of different quarantine strategies on outbreak containment within RCHs. The significant difference in contact hours between weekdays and weekends was observed for some pairs of RCH residents and staff during the two-week data collection period. No significant difference between secondary cases and uninfected contacts was observed in a COVID-19 outbreak in terms of their demographics and contact patterns. Simulation results based on the collected contact data indicated that a threshold of accumulative contact hours one or two days prior to diagnosis of the index case could dramatically increase the efficiency of outbreak containment within RCHs by targeted isolation of the close contacts. This study demonstrated the feasibility and efficiency of employing an AI-empowered system in indoor digital contact tracing of outbreaks in RCHs in the post-pandemic era.
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Background: Vaccination has been the most important measure to mitigate the COVID-19 pandemic. The vaccination coverage was relatively low in Hong Kong Special Administrative Region China, compared to Singapore, in early 2022. Hypothetically, if the two regions, Hong Kong (HK) and Singapore (SG), swap their vaccination coverage rate, what outcome would occur? Method: We adopt the Susceptible - Vaccinated - Exposed - Infectious - Hospitalized - Death - Recovered model with a time-varying transmission rate and fit the model to weekly reported COVID-19 deaths (the data up to 2022 Nov 4) in HK and SG using R package POMP. After we obtain a reasonable fitting, we rerun our model with the estimated parameter values and swap the vaccination rates between HK and SG to explore what would happen. Results: Our model fits the data well. The reconstructed transmission rate was higher in HK than in SG in 2022. With a higher vaccination rate as in SG, the death total reported in HK would decrease by 37.5% and the timing of the peak would delay by 3 weeks. With a lower vaccination rate as in HK, the death total reported in SG would increase to 5.5-fold high with a peak 6 weeks earlier than the actual during the Delta variant period. Conclusions: Vaccination rate changes in HK and SG may lead to very different outcomes. This is likely due that the estimated transmission rates were very different in HK and SG which reflect the different control policies and dominant variants. Because of strong control measures, HK avoided large-scale community transmission of the Delta variant. Given the high breakthrough infection rate and transmission rate of the Omicron variant, increasing the vaccination rate in HK will likely yield a mild (but significant) contribution in terms of lives saved. While in SG, lower vaccination coverage to the level of HK will be disastrous.
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Laryngeal squamous cell cancer (LSCC) is one of the most common malignant tumors in head and neck tumors. Our previous study has revealed that hsa_circ_0006232 is abnormally expressed in LSCC. This study attempts to verify the biological role of hsa_circ_0006232 in LSCC. We found that compared with human bronchial epithelial cells, hsa_circ_0006232 was highly expressed in human LSCC cells (AMC-HN-8 and TU686). Moreover, hsa_circ_0006232 promoted proliferation, migration and invasion of AMC-HN-8 and TU686 cells. Hsa_circ_0006232 promoted the expression of enhancer of zeste homolog 2 (EZH2) and repressed the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Fused in sarcoma (FUS) interacted with hsa_circ_0006232 and EZH2, and FUS promoted the stabilization of EZH2. Hsa_circ_0006232 inhibited PTEN by promoting FUS expression. Moreover, we constructed a tumor xenograft model by injection of AMC-HN-8 cells with hsa_circ_0006232 knockdown, and we found that hsa_circ_0006232 deficiency decreased tumor growth in mice. Hsa_circ_0006232 silencing repressed EZH2 expression and enhanced PTEN expression in tumor tissues. In conclusion, our data have demonstrated that Hsa_circ_0006232 promotes proliferation, migration and invasion of LSCC cells, and accelerates tumor growth of LSCC through FUS-mediated EZH2 stabilization. Thus, hsa_circ_0006232 may be a novel therapeutic target in LSCC treatment.
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Carcinogênese/metabolismo , Progressão da Doença , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Neoplasias Laríngeas/metabolismo , RNA Circular/metabolismo , Proteína FUS de Ligação a RNA/metabolismo , Transdução de Sinais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Animais , Brônquios/citologia , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Células Epiteliais/metabolismo , Inativação Gênica , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , RNA Circular/genética , Proteína FUS de Ligação a RNA/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Transfecção , Carga Tumoral/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumour of the head and neck. Our previous study reveals that the circular RNA (circRNA) hsa_circ_0042823 is abnormally expressed in LSCC, suggesting that hsa_circ_0042823 is closely associated with LSCC. Here, we attempted to explore the molecular mechanism of hsa_circ_0042823 in LSCC. METHODS: Quantitative real-time PCR and western blot were performed to assess the expression of gene and protein in human laryngeal carcinoma cells, TU212 and TU686. MTT and transwell assays were performed to examine cell proliferation, migration and invasion. The relationship among hsa_circ_0042823, miR-877-5p and forkhead box M1 (FOXM1) was verified by luciferase reporter assay. Finally, we constructed a subcutaneous tumour mouse model to analyse in vivo growth of LSCC cells following knockdown of hsa_circ_0042823. RESULTS: Compared with normal human bronchial epithelial cells (HBECs), hsa_circ_0042823 was highly expressed in the LSCC cell lines (AMC-HN-8 and TU686). Further studies demonstrated that hsa_circ_0042823 interacted with miR-877-5p, and FOXM1 was the target of miR-877-5p. Hsa_circ_0042823 promoted the expression of FOXM1 via its ceRNA activity on miR-877-5p. Hsa_circ_0042823 overexpression promoted proliferation, migration and invasion of AMC-HN-8 cells through regulating miR-877-5p/FOXM1 axis. Additionally, inhibition of hsa_circ_0042823 inhibited growth of LSCC in vivo via miR-877-5p/FOXM1 axis. CONCLUSIONS: Hsa_circ_0042823/miR-877-5p/FOXM1 axis participates in the progression of LSCC. This work demonstrates that hsa_circ_0042823 accelerates cancer progression by regulating miR-877-5p/FOXM1 axis in LSCC. Therefore, this study may provide new insights into the pathogenesis of LSCC.KEY MESSAGESHsa_circ_0042823 promotes FOXM1 expression by sponging miR-877-5p.Hsa_circ_0042823 promotes proliferation, migration, invasion of LSCC cells.Hsa_circ_0042823 knockdown inhibits tumour growth of LSCC via miR-877-5p/FOXM1 axis.
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Proteína Forkhead Box M1 , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , MicroRNAs , Carcinoma de Células Escamosas de Cabeça e Pescoço , Animais , Proliferação de Células/genética , Progressão da Doença , Proteína Forkhead Box M1/genética , Neoplasias de Cabeça e Pescoço/genética , Humanos , Neoplasias Laríngeas/genética , Camundongos , MicroRNAs/genética , RNA Circular , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
Accumulating evidence suggests that circular RNAs (circRNAs) may be a key contributor to oncogenesis. Yet, the function of circRNAs in laryngeal squamous cell carcinoma (LSCC) is still not clear. In this study, we examined the function of circRNA_103862 in LSCC progression by analyzing the tissue specimens collected from a patient with LSCC by using different LSCC cell models in vitro and an LSCC xenograft model in nude mice. We found that circRNA_103862 was frequently upregulated in the tissues of LSCC and was correlated with metastasis and prognosis of LSCC patients. Furthermore, circRNA_103862 downregulation could reduce proliferation, migration, and invasion ability of LSCC cells. In terms of mechanism exploration, miR-493-5p was sponged by circRNA_103862. Rescue experiments also showed that circRNA_103862 could achieve a carcinogenic effect by regulating miR-493-5p. Moreover, a luciferase reporter analysis showed that Golgi membrane protein 1 (GOLM1) is a downstream effector of miR-493-5p. In conclusion, our data suggested that circRNA_103862 promotes the proliferation of LSCC through targeting the miR-493-5p/GOLM1 axis, and it might serve as a potential prognosis marker and therapy target for LSCC.
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Long non-coding RNAs (lncRNAs) play important roles in various biological progresses of carcinogenesis. However, the function of lncRNAs in human sinonasal squamous cell carcinoma (SNSCC) remains greatly unclear. In the current study, lncRNA AC091729.7 expression was examined in SNSCC samples by using microarray, RNA in situ hybridization (ISH) and real-time fluorescence quantitative PCR (qRT-PCR). Cell viability, colony-formation, wound-healing, and transwell assays were applied to SNSCC cells. Xenograft mouse models were employed to evaluate the role of AC091729.7 in growth of SNSCC in vivo. Human protein microarray (HuprotTM Protoarray) and RNA immunoprecipitation (RIP) were used for identifying AC091729.7 binding proteins in SNSCC. Results showed AC091729.7 was upregulated and closely connected with the survival of the SNSCC patients. Knockdown of AC091729.7 suppressed SNSCC cell migration, proliferation, invasion in vitro. Furthermore, downregulation of AC091729.7 could inhibit the growth of SNSCC in vivo. Moreover, Human protein microarray and RIP suggested that AC091729.7 directly combine with the serine/arginine rich splicing factor 2 (SRSF2). Our results suggest that in the cell progression of SNSCC, lncRNA AC091729.7 plays a carcinogenic role and serves as a novel biomarker and latent curative target in SNSCC patients.