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tRNA-derived small RNAs (tsRNAs) are novel non-coding RNAs that are involved in the occurrence and progression of diverse diseases. However, their exact presence and function in hepatocellular carcinoma (HCC) remain unclear. Here, differentially expressed tsRNAs in HCC were profiled. A novel tsRNA, tRNAGln-TTG derived 5'-tiRNA-Gln, is significantly downregulated, and its expression level is correlated with progression in patients. In HCC cells, 5'-tiRNA-Gln overexpression impaired the proliferation, migration, and invasion in vitro and in vivo, while 5'-tiRNA-Gln knockdown yielded opposite results. 5'-tiRNA-Gln exerted its function by binding eukaryotic initiation factor 4A-I (EIF4A1), which unwinds complex RNA secondary structures during translation initiation, causing the partial inhibition of translation. The suppressed downregulated proteins include ARAF, MEK1/2 and STAT3, causing the impaired signaling pathway related to HCC progression. Furthermore, based on the construction of a mutant 5'-tiRNA-Gln, the sequence of forming intramolecular G-quadruplex structure is crucial for 5'-tiRNA-Gln to strongly bind EIF4A1 and repress translation. Clinically, 5'-tiRNA-Gln expression level is negatively correlated with ARAF, MEK1/2, and STAT3 in HCC tissues. Collectively, these findings reveal that 5'-tiRJNA-Gln interacts with EIF4A1 to reduce related mRNA binding through the intramolecular G-quadruplex structure, and this process partially inhibits translation and HCC progression.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Fator de Iniciação 4A em Eucariotos/genética , Linhagem Celular , RNA de Transferência/química , RNA de Transferência/genética , RNA de Transferência/metabolismo , RNA , Proliferação de CélulasRESUMO
Transfer RNA-derived fragments are a group of small noncoding single-stranded RNA that play essential roles in multiple diseases. However, their biological functions in carcinogenesis are not well understood. In this study, 5'tRF-Gly was found to have significantly high expression in hepatocellular carcinoma (HCC), and the upregulation of 5'tRF-Gly was positively correlated with tumor size and tumor metastasis. Overexpression of 5'tRF-Gly induced increased growth rate and metastasis in HCC cells in vitro and in nude mice, while knockdown showed the opposite effect. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was confirmed to be a direct target of 5'tRF-Gly in HCC. In addition, the cytological effect of CEACAM1 knockdown proved to be similar to the overexpression of 5'tRF-Gly. Moreover, attenuation of CEACAM1 expression rescued the 5'tRF-Gly-mediated promoting effects on HCC cells. These data show that 5'tRF-Gly is a new tumor-promoting factor and could be a potential diagnostic biomarker or new therapeutic target for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Animais , Antígenos CD , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/metabolismo , Carcinoma Hepatocelular/patologia , Molécula 1 de Adesão Celular/metabolismo , Moléculas de Adesão Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , RNA , RNA Longo não Codificante/genética , RNA de TransferênciaRESUMO
Drought stress can negatively impact crop yield and quality. Improving wheat yields under drought stress is a major objective of agronomic research. Glutamine synthetase (GS) is a key enzyme of nitrogen metabolism that is critical to plant growth and development in abiotic stress response. However, to date, no systemic characterization of the GS genes has yet been conducted in wheat and its close relatives. We identified a total of 15 GS genes in Triticum aestivum (2n = 6x = 42; AABBDD), as well as 9 GS genes in Triticum dicoccoides (2n = 4x = 28; AABB), 6 in Aegilops tauschii (2n = 2x = 14; DD), and 5 in Triticum urartu (2n = 2x = 14; AA). The 35 GSs were further clustered into five lineages according to the phylogenetic tree. Synteny analysis revealed that the three subgenomes in bread wheat retained extensive synteny between bread wheat and its three relative species. We identified three up-regulated TaGSs (Ta4A.GSe, Ta4B.GSe, and Ta4D.GSe) from transcriptome data after drought and salt stress. Ta4D.GSe was subsequently used for further functional studies, and its subcellular localization were determined in Arabidopsis protoplasts. Its overexpression in Arabidopsis enhanced drought tolerance by increasing the ability of scavenging of reactive oxygen species (ROS) and osmotic adjustment. We identified GS gene family in four wheat species and performed comparative analyses of their relationships, chromosome locations, conserved motif, gene structure, and synteny. The subcellular localization of Ta4D.GSe was detected and its drought tolerance function was demonstrated. Taken together, these findings provide insight into the potential functional roles of the GS genes in abiotic stress tolerance. KEY MESSAGE: This report clearly shows detailed characterization of GS gene family in four wheat species and demonstrates that Ta4D.GSe plays an important role in enhancing drought tolerance by improving the scavenging of ROS and osmotic adjustment ability in Arabidopsis.
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Arabidopsis , Triticum , Arabidopsis/genética , Secas , Regulação da Expressão Gênica de Plantas , Glutamato-Amônia Ligase/genética , Filogenia , Proteínas de Plantas/genética , Espécies Reativas de Oxigênio , Estresse Fisiológico/genética , Triticum/genéticaRESUMO
PURPOSE: The purpose of this study was to evaluate the diagnostic performance of novel ultrasound technology normalized local variance (NLV) and the standard deviation of NLV (NLV-SD) using different ROIs for hepatic steatosis in patients with metabolic-associated fatty liver disease (MAFLD) and to identify the factors that influence the NLV value and NLV-SD value, using pathology results as the gold standard. METHODS: We prospectively enrolled 34 consecutive patients with suspected MAFLD who underwent percutaneous liver biopsy for evaluation of hepatic steatosis from June 2020 to December 2020. All patients underwent ultrasound and NLV examinations. NLV values and NLV-SD values were measured using different ROIs just before the liver biopsy procedure. RESULTS: The distribution of hepatic steatosis grade on histopathology was 4/19/6/5 for none (< 5%)/ mild (5-33%)/ moderate (> 33-66%)/ and severe steatosis (> 66%), respectively. The NLV value with 50-mm-diameter ROI and NLV-SD value with 50-mm-diameter ROI showed a significant negative correlation with hepatic steatosis (spearman correlation coefficient: - 0.449, p = 0.008; - 0.471, p = 0.005). The AUROC of NLV (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.875, 0.735, and 0.583, respectively. The AUROC of NLV-SD (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.900, 0.745, and 0.603, respectively. NLV (50 mm) values and NLV-SD (50 mm) values between two readers showed excellent repeatability and the intraclass correlation coefficient (ICC) was 0.930 (p < 0.001) and 0.899 (p < 0.001). Hepatic steatosis was the only determinant factor for NLV value and NLV-SD value (p = 0.012, p = 0.038). CONCLUSION: The NLV (50 mm) and NLV-SD (50 mm) provided good diagnostic performance in detecting the varying degrees of hepatic steatosis with great reproducibility. This study showed that the degree of steatosis was the only significant factor affecting the NLV value and NLV-SD value.
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Fígado Gorduroso , Fígado , Biópsia , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/patologia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Projetos Piloto , Reprodutibilidade dos Testes , Tecnologia , Ultrassonografia/métodosRESUMO
OBJECTIVE: We investigated lenvatinib plus programmed cell death-1 (PD-1) inhibitors as a first-line treatment for initially unresectable biliary tract cancer (BTC). METHODS: In this Phase II study, adults with initially unresectable BTC received lenvatinib (body weight ≥60 kg, 12 mg; <60 kg, 8 mg) daily and PD-1 inhibitors (pembrolizumab/tislelizumab/sintilimab/camrelizumab 200 mg or toripalimab 240 mg) every 3 weeks. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included surgical conversion rate, disease control rate (DCR), event-free survival (EFS), overall survival (OS) and tumor biomarkers. RESULTS: Among 38 enrolled patients, the ORR was 42.1% and the DCR was 76.3%. Thirteen (34.2%) patients achieved downstaging and underwent surgery, six of whom (46.2%) achieved a major pathologic response (n=2) or partial pathologic response (n=4) in the primary tumor. In total, 84.2% of patients experienced ≥1 treatment-related adverse event (TRAE), 34.2% experienced a Grade ≥3 TRAE and no treatment-related deaths occurred. After a median follow-up of 13.7 months the median EFS was 8.0 months (95% CI: 4.6-11.4) and the median OS was 17.7 months (95% CI: not estimable). CONCLUSIONS: Lenvatinib plus PD-1 inhibitors showed promising anti-tumor efficacy in patients with initially unresectable BTC and was generally well tolerated. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, ChiCTR2100044476.
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BACKGROUND: Circular RNAs (circRNAs), which are endogenous non-coding RNAs, are associated with various biological processes including development, homeostatic maintenance, and pathological responses. Accumulating evidence has implicated non-coding RNAs in cancer progression, and the role of circRNAs in particular has drawn wide attention. However, circRNA expression patterns and functions in hepatocellular carcinoma (HCC) remain poorly understood. METHODS: CircRNA sequencing was performed to screen differentially expressed circRNAs in HCC. Northern blotting, quantitative real-time polymerase chain reaction, nucleocytoplasmic fractionation, and fluorescence in situ hybridization analyses were conducted to evaluate the expression and localization of circSLC7A11 in HCC tissues and cells. CircSLC7A11 expression levels were modified in cultured HCC cell lines to explore the association between the expression of circSLC7A11 and the malignant behavior of these cells using several cell-based assays. The modified cells were implanted into immunocompetent nude mice to assess tumor growth and metastasis in vivo. We applied bioinformatics methods, RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays to explore the mechanisms of circSLC7A11 in HCC. RESULTS: CircSLC7A11 (hsa_circ_0070975) was conserved and dramatically overexpressed in HCC tissues and cells. HCC patients showing high circSLC7A11 expression had worse prognoses. Our in vitro and in vivo experiments showed that circSLC7A11 markedly accelerated HCC progression and metastasis through the circSLC7A11/miR-330-3p/CDK1 axis. CONCLUSIONS: The acceleration of HCC progression and metastasis by circSLC7A11 through the circSLC7A11/miR-330-3p/CDK1 axis suggests that circSLC7A11 is a potential novel diagnostic and therapeutic target for HCC treatment.
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Soil salinization is one of the major abiotic stresses that adversely affect the yield and quality of crops such as wheat, a leading cereal crop worldwide. Excavating the salt-tolerant genes and exploring the salt tolerance mechanism can help breeding salt-tolerant wheat varieties. Thus, it is essential to identify salt-tolerant wheat germplasm resources. In this study, we carried out a salt stress experiment using Qing Mai 6 (QM6), a salt-tolerant wheat variety, and sequenced the miRNAs and mRNAs. The differentially expressed miRNAs and mRNAs in salt stress conditions were compared with the control. As results, a total of eight salt-tolerance-related miRNAs and their corresponding 11 target mRNAs were identified. Further analysis revealed that QM6 enhances salt tolerance through increasing the expression level of genes related to stress resistance, antioxidation, nutrient absorption, and lipid metabolism balance, and the expression of these genes was regulated by the identified miRNAs. The resulting data provides a theoretical basis for future research studies on miRNAs and novel genes related to salt tolerance in wheat in order to develop genetically improved salt-tolerant wheat varieties.
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OBJECTIVE: To evaluate the influence of evidence-based nursing (EBN) on psychological well-being, postoperative complications and quality of life (QOL) after breast cancer (BC) surgery. METHODS: A total of 263 patients with BC who were surgically treated in Zhejiang Provincial People's Hospital from May, 2018 to August, 2019 were as assigned to observation group (EBN, n=142) and control group (routine nursing care, n=121). Clinical indicators and any complications after intervention were recorded. And the exercise compliance in the affected limbs was evaluated. Barthel index (BI), self-rating anxiety scale (SAS) and self-rating depression scale (SDS), Pittsburgh Sleep Quality Index (PSQI) were employed for the assessment of self-care ability, psychological status, and sleep quality, respectively. In addition, we utilized the numerical rating scale (NRS) to evaluate postoperative pain, the functional assessment of cancer therapy-breast (FACT-B) scale to assesse the quality of life (QOL), and the self-made questionnaire to quantify patient satisfaction. RESULTS: After intervention, the observation group presented greater improvement in symptoms, higher exercise compliance and BI scores, as well as lower SAS, SDS, and PSQI scores; the incidence of postoperative pain and complications decreased in observation group, and FACT-B scores and patient satisfaction increased. CONCLUSION: EBN is effective in relieving symptoms, reducing negative emotions and postoperative complications, as well as enhancing the QOL of patients undergoing BC surgery.
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PURPOSE: Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver primary tumors but its treatments are limited. Bioinformatics showed that the expression level of long non-coding RNA cancer-associated susceptibility 15 gene (CASC15) is correlated with ICC progression, but its functional mechanism remains unclear. MATERIALS AND METHODS: Tissues from ICC patients, tumor and adjacent tissue, were used for detection of the expression of CASC15. Clinical data were also collected for clinicopathologic and survival analysis. Short interfering RNA and lentiviral short hairpin RNA were used to knock down CASC15 and PRDX2 expression in ICC cell lines, for the analysis of changes of cell function and xenografts. RNA-pulldown and RNA immunoprecipitation assays were used to detect RNA-binding protein, PRDX2. Male nude mice were used for ICC xenografts, and livers were collected after 4 weeks for immunohistochemistry. RESULTS: CASC15 is highly expressed in ICC tissues and is related to higher TNM stage. Knockdown of CASC15 in ICC cells reduced cell proliferation, migration, invasiveness and increased apoptosis, and G1/S block. PRDX2 bound to CASC15. Knockdown of CASC15 decreased PRDX2 expression which was rescued by the inhibition of proteasome formation. Downregulation of PRDX2 resulted in G1/S block, reduced ICC cell invasion. Downregulation of CASC15 inhibited phosphoinositide 3-kinase (PI3K)/AKT/c-Myc pathway through downregulating of PRDX2 and overexpressed PRDX2 rescued the block. CASC15 knockout in ICC xenografts suppressed tumor development in vivo, decreased the expression of PRDX2 and Ki67 and inhibited PI3K/AKT pathway. CONCLUSION: CASC15 promotes ICC possibly by targeting PRDX2 via the PI3K/AKT pathway, indicating poor prognosis and high degree of malignancy of ICC.
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Colangiocarcinoma/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , TransfecçãoRESUMO
[This retracts the article DOI: 10.21037/atm.2019.10.113.].
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Background and Aims: The best treatment modalities for elderly patients with stage I-II HCC (hepatocellular carcinoma) remain controversial in an era of a shortage of liver donors. Methods: From the SEER database (Surveillance, Epidemiology, and End Results program), 2,371 elderly patients were sampled as Cohort 1. OS (Overall Survival) and CSS (Cancer-Specific Survival) were compared between the Non-surgery and Surgery groups. A stratification analysis in a CSS Cox model was also conducted among sub-groups, and propensity score matching was performed to generate Cohort 2 (746 pairs), reducing the influences of confounders. Results: For Cohort 1, the median follow-up times of the Non-surgery and Surgery groups were 11 months (95% CI, confidence interval: 9.74-12.26) vs. 49 months (44.80-53.21) in OS, and 14 months (12.33-15.67) vs. 74 months (64.74-83.26) in CSS, respectively. In the stratification analysis, for the elderly patients (age >= 70 years), Larger Resection was associated with a higher HR (hazard ratio) than Segmental Resection: 0.30 (95% CI, confidence interval: 0.22-0.41) vs. 0.29 (0.21-0.38) in 70-74 year-olds; 0.26 (0.18-0.38) vs. 0.23 (0.16-0.32) in 75-79 year-olds; 0.32 (0.21-0.49) vs. 0.21 (0.13-0.32) in those 80+ years old. For Cohort 2, a similar result could be seen in the CSS Cox forest plot. The HRs of Larger Resection and Segmental Resection were 0.27 (0.21-0.33) and 0.25 (0.20-0.31), respectively. Conclusions: It is cautiously recommended that, when liver transplantation is not available, segmental or wedge liver resection is the better treatment choice for elderly patients with stage I-II HCC (AJCC edition 6), especially those over 70 years old, compared with other surgeries, based on the SEER data.
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Mitochondrial diseases are a group of clinically and genetically heterogeneous disorders driven by oxidative phosphorylation dysfunction of the mitochondrial respiratory chain which due to pathogenic mutations of mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Recent progress in molecular genetics and biochemical methodologies has provided a better understanding of the etiology and pathogenesis of mitochondrial diseases, and this has expanded the clinical spectrum of this conditions. But the treatment of mitochondrial diseases is largely symptomatic and thus does not significantly change the course of the disease. Few clinical trials have led to the design of drugs aiming at enhancing mitochondrial function or reversing the consequences of mitochondrial dysfunction which are now used in the clinical treatment of mitochondrial diseases. Several other drugs are currently being evaluated for clinical management of patients with mitochondrial diseases. In this review, the current status of treatments for mitochondrial diseases is described systematically, and newer potential treatment strategies for mitochondrial diseases are also discussed.
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Integrin subunit alpha 3 (ITGA3) interacts with a beta 1 subunit to form a member of the integrin family. Integrins are heterodimeric integral membrane proteins that serve as cell surface adhesion proteins. In this research, we investigated the biological function of this protein in human intrahepatic cholangiocarcinoma (ICC) for the first time. Here, using Western blotting and immunohistochemistry assays, we discovered that ITGA3 was overexpressed in ICC cell lines and ICC patients. Moreover, we found ITGA3 expression correlated with several clinicopathological features, including tumor size, lymph node metastasis, and the TNM stage. Patients with high ITGA3 expression underwent a worse prognosis after complete resection compared with patients with low ITGA3 expression in terms of overall survival. Furthermore, we demonstrated that ITGA3 could significantly promote ICC cell proliferation and cell cycle progression in vitro. However, as a classical cell surface adhesion molecule, we found ITGA3 correlated negatively with the migration and invasion of ICC cell lines, which differs from other malignant tumors. Generally, these findings suggest that ITGA3 may play a role as a potential oncogene in ICC and suppression of ITGA3 expression may establish a novel target for guiding the therapy of ICC patients.
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Biomarcadores Tumorais/genética , Colangiocarcinoma/genética , Integrina alfa3/genética , Prognóstico , Adulto , Idoso , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Colangiocarcinoma/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
Several long non-coding RNAs (lncRNAs) play important roles in the regulation of liver metastasis in colorectal cancer (CRC) patients. We previously described the potential involvement of HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS), miR-125a-5p, and peptidyl arginine deiminase 2 (PADI2) in promoting liver metastasis in CRC patients. In the present study, we verified the significant upregulation of HOXA11-AS and PADI2, as well as the downregulation of miR-125a-5p, in CRC patients with liver metastasis. Overexpression and knockdown studies of HOXA11-AS or PADI2, as well as gain-/loss-of-function studies of miR-125a-5p, revealed a positive correlation between HOXA11-AS and PADI2 and a negative correlation with miR-125a-5p in the regulation of liver metastasis in CRC cell lines. Overall, we conclude that HOXA11-AS promotes liver metastasis in CRC by functioning as a miR-125a-5p sponge and describe a novel HOXA11-AS-miR-125a-5p-PADI2 regulatory network involved in CRC liver metastasis.
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Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for one-sixth of all malignant tumors, and the mortality rate of HCC ranks second among all cancer-related deaths. Increasing evidence has recently shown that long non-coding RNAs (lncRNAs) play an important role in cancer occurrence and progression, including HCC. Cancer susceptibility candidate 15 (CASC15), a lncRNA, has been reported to be involved in melanoma progression and phenotype switching. However, the function of CASC15 in human HCC is still unknown. In the present study, we evaluated expression of CASC15 and its potential functions in HCC. The expression of CASC15 in HCC tissues was quantitated by the reverse-transcription quantitative polymerase chain reaction, which showed that CASC15 was overexpressed in 59% (48/82) of HCC tissues compared with corresponding adjacent normal tissues, and the CASC15 expression level was significantly correlated with metastasis (P=0.012), tumor size (P=0.037), and TNM stage (P=0.013). Kaplan-Meier survival curves showed that high CASC15 expression was associated with poor prognosis in HCC patients (P<0.05). Moreover, a knockdown model of CASC15 was established, which showed that CASC15 significantly impaired HCC cell proliferation, migration, and invasion. CASC15 knockdown also induced cell apoptosis in vitro and impaired tumor growth in vivo. In conclusion, CASC15 plays an important role in the progression of HCC, acting as an oncogene. High expression of CASC15 is correlated with a poor prognosis, suggesting that CASC15 may be a predictive biomarker of HCC.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA não Traduzido/genética , Animais , Carcinogênese/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Técnicas de Silenciamento de Genes , Células Hep G2 , Xenoenxertos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Estadiamento de Neoplasias , RNA não Traduzido/biossíntese , RNA não Traduzido/metabolismo , Regulação para CimaRESUMO
In early studies, it was shown that HINT2, which sensitizes cells to mitochondrial apoptosis, is down-regulated in hepatocellular carcinoma (HCC) cells (Martin et al., 2006). However, the molecular mechanism of this effect is unknown. Immunohistochemistry revealed that HINT2 expression is relatively low in pancreatic cancer tissues, compared to that in adjacent tissues (P < 0.05). Furthermore, its expression was related to pathological grade and lymph node metastasis (P = 0.0161 and 0.0108, respectively); in addition, down-regulation of HINT2 was found to be associated with relatively poor prognosis in pancreatic cancer patients. Up-regulation of HINT2 was shown to trigger pancreatic cancer cell apoptosis, decrease mitochondrial membrane potential (ΔΨm), promote intracellular reactive oxygen species (ROS) production, and elevate mitochondrial Ca2+ levels. However, co-treatment of HINT2 overexpressing BxPC-3 cells with ruthenium red partially inhibited HINT2-induced apoptosis, which was associated with a reduction in ΔΨm and an increase in intracellular ROS and mitochondrial Ca2+. According to our results, mitochondrial calcium uptake1 and 2 (MICU1 and MICU2) were down-regulated and the essential MCU regulator (EMRE) was up-regulated in cells transduced with Adv-HINT2. Therefore, we deduced that HINT2 triggers apoptosis in pancreatic cancer cells by regulating mitochondrial Ca2+ influx through the mitochondrial calcium uniporter (MCU). In addition, we found that HINT2 can sensitize BxPC-3 and L3.6pl cells to gemcitabine-induced apoptosis and that gemcitabine up-regulates HINT2 expression. This indicates that gemcitabine-induced apoptosis is related to HINT2 levels.
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Antimetabólitos Antineoplásicos/farmacologia , Canais de Cálcio/metabolismo , Desoxicitidina/análogos & derivados , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Desoxicitidina/farmacologia , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Mitocondriais/biossíntese , Neoplasias Pancreáticas/genética , GencitabinaRESUMO
Pseudogenes are a subclass of long non-coding (lnc) RNAs that arose from protein-coding genes, but have lost the ability to produce proteins. Pseudogenes play an important role in the pathogenesis of various tumors; however, the role of pseudogenes in hepatocellular carcinoma (HCC) is poorly understood. In this study, we investigated a novel pseudogene, PDIA3P1, which was upregulated in HCC tissues compared with paired normal adjacent tissues. The expression of PDIA3P1 was significantly correlated with tumor size, metastasis, TNM stage, and overall stage. Knockdown of PDIA3P1decreased proliferation, migration, and invasion of HCC cells. PDIA3P1 knockdown also promoted cell apoptosis and inhibited tumor growth in vivo. We performed a GeneChip assay to investigate the underlying mechanism of PDIA3P1 action on biological function, and our results suggested that PDIA3P1 may promote proliferation and inhibit apoptosis of liver cancer cells by inhibiting the p53 pathway. Thus, our data suggest that PDIA3P1 acts as an oncogene in HCC and could be a potential prognostic marker and therapeutic target for HCC.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Isomerases de Dissulfetos de Proteínas/fisiologia , RNA Longo não Codificante/fisiologia , Proteína Supressora de Tumor p53/metabolismo , Idoso , Animais , Apoptose/fisiologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Invasividade Neoplásica , Isomerases de Dissulfetos de Proteínas/metabolismo , Análise de Sobrevida , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genéticaRESUMO
The diploid species G. herbaceum (A1) and G. raimondii (D5) are the progenitors of allotetraploid cotton, respectively. However, hybrids between G. herbaceum and G. raimondii haven't been reported. In the present study, hybridization between G. herbaceum and G. raimondii was explored. Morphological, cytogenetic and molecular analyses were used to assess the hybridity. The interspecific hybrid plants were successfully obtained. Most of the morphological characteristics of the hybrids were intermediate between G. herbaceum and G. raimondii. However, the color of glands, anther cases, pollen and corolla, and the state of bracteoles in hybrids were associated with the G. herbaceum. The color of staminal columns and filaments in hybrids were associated with G. raimondii. Cytogenetic analysis confirmed abnormal meiotic behavior existed in hybrids. The hybrids couldn't produce boll-set. Simple sequence repeat results found that besides the fragments inherited from the two parents, some novel bands were amplified in hybrids, indicating that potential mutations and chromosomal recombination occurred between parental genomes during hybridization. These results may provide some novel insights in speciation, genome interaction, and evolution of the tetraploid cotton species.
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Gossypium/genética , Hibridização Genética , Melhoramento Vegetal/métodos , Mutação , Ploidias , Característica Quantitativa Herdável , Recombinação GenéticaRESUMO
Long noncoding RNAs (lncRNAs) play crucial roles in cancer occurrence and progression. However, the relationship between the expression levels of lncRNAs and the hepatocellular carcinoma (HCC) process is unclear. The goal of this study was to determine the expression level of ZNF674-AS1, a newly found lncRNA, in HCC and its clinical association. The expression of ZNF674-AS1 in 137 pairs of tumorous and adjacent normal tissues from patients with HCC was detected by quantitative real-time reverse transcription polymerase chain reaction. Additionally, the potential associations between its level in HCC tissue and clinicopathological features were analyzed. The expression of ZNF674-AS1 in the HCC cell lines HepG2, HCCLM3, SK-Hep1, HuH7, Hep3B, and MHCC97H was significantly downregulated compared with that in the normal liver cell line QSG-7701. The expression of ZNF674-AS1 was downregulated in 72% (99/137) of HCC tissues compared with that in paired adjacent normal tissues (p < 0.01). The results showed that the ZNF674-AS1 expression level was significantly correlated with metastasis (p = 0.041), clinical stage (p = 0.039), and histopathologic grading (p = 0.045). In addition, the Kaplan-Meier survival curves revealed that low ZNF674-AS1 expression was associated with poor prognosis in patients with HCC. Our data suggest that ZNF674-AS1 may play some role during cancer occurrence and progression and may be a new biomarker for HCC.