ABSTRACT
OBJECTIVE: In this study, we aimed to investigate the function of microRNA-373-3p (miR-373-3p) in the pathogenesis of cervical cancer. METHODS: Human and mouse cervical cancer cell lines were transfected with miR-373-3p mimic and inhibitor. Cell proliferation and viability were evaluated with Cell Counting Kit-8 (CCK-8) assay and Lactate Dehydrogenase (LDH) assay, respectively. The AKT1-targeting role of miR-373-3p was analyzed by qPCR and Western blot. Finally, a mouse xenograft cervical tumor model was adopted to study the in vivo effect of miR-373-3p on tumor growth and the expression of AKT1. RESULTS: Over-expression of miR-373-3p significantly reduced the proliferation of cervical carcinoma cell line in vitro. In addition, miR-373-3p overexpression also inhibited cervical cancer growth in tumor-bearing mice. Mechanistically, we found that AKT1 gene can be targeted by miR-373-3p. MiR-373-3p mimic decreased the mRNA and protein expression of AKT1, while the miR-373-3p inhibitor increased the level of AKT1 in cervical cancer cells. AKT1 overexpression rescued the proliferation of cervical cancer cells transfected with miR-373-3p. CONCLUSION: MiR-373-3p can serve as a novel anti-tumor microRNA in cervical cancer by targeting AKT1.
Subject(s)
Cell Proliferation/genetics , MicroRNAs/physiology , Proto-Oncogene Proteins c-akt/genetics , Uterine Cervical Neoplasms/pathology , Animals , Cell Line, Tumor , Disease Progression , Down-Regulation , Female , Heterografts , Humans , Mice , Mice, Inbred C57BL , Uterine Cervical Neoplasms/enzymologyABSTRACT
Objective To evaluate the clinical efficacy of tiotropium combined with large dose salmeterol/fluticasone in the treatment of severe bronchial asthma with chronic obstructive pulmonary disease (COPD). Methods 60 patients with severe bronchial asthma with COPD stabilization in Taizhou hospital of Zhejiang province from January 2015 to December 2016 were selected and divided into the control and the study group according to the time of visiting hospital,30 cases in each group. The control group were given large dose Salmeterol/fluticasone on the basis of conventional treatment, the study group were treated with tiotropium bromide on the basis of control group. Results FEV1、FVC、FEV1/FVC、PEF and pulmonary function index were compared before the treatment between two groups. After treatment,FEV1,FVC,FEV1/FVC、PEF and pulmonary function index in the study group were better than the control group (P<0.05). Conclusion The combination of tiotropium and large dose salmeterol/fluticasone can significantly improve the clinical efficacy in the treatment of severe bronchial asthma and chronic obstructive pulmonary disease.
ABSTRACT
Objective To evaluate the clinical efficacy of tiotropium combined with large dose salmeterol/fluticasone in the treatment of severe bronchial asthma with chronic obstructive pulmonary disease (COPD). Methods 60 patients with severe bronchial asthma with COPD stabilization in Taizhou hospital of Zhejiang province from January 2015 to December 2016 were selected and divided into the control and the study group according to the time of visiting hospital,30 cases in each group. The control group were given large dose Salmeterol/fluticasone on the basis of conventional treatment, the study group were treated with tiotropium bromide on the basis of control group. Results FEV1、FVC、FEV1/FVC、PEF and pulmonary function index were compared before the treatment between two groups. After treatment,FEV1,FVC,FEV1/FVC、PEF and pulmonary function index in the study group were better than the control group (P<0.05). Conclusion The combination of tiotropium and large dose salmeterol/fluticasone can significantly improve the clinical efficacy in the treatment of severe bronchial asthma and chronic obstructive pulmonary disease.
ABSTRACT
Cervical cancer is one of the most lethal malignancies amongst women, partially because it is unresponsive to many chemotherapeutic drugs. The mechanism underlying cisplatin (DDP) resistance in cervical cancer remains largely elusive. In this study, by detecting the 12 most reported down-regulated miRNAs in chemotherapy-sensitive and -resistant cervical cancer cells, we found that miR-497 was significantly reduced in chemotherapy-resistant HeLa/DDP cells and contributed to DDP chemosensitivity. Transketolase (TKT), a thiamine-dependent enzyme that plays a role in the channeling of excess glucose phosphates to glycolysis in the pentose phosphate pathway, was identified as a direct target of miR-497. TKT expression in clinical specimens was characterized by immunohistochemistry and the result showed that TKT was highly expressed in 81.1% (60/74) of samples examined. Data from Oncomine databases revealed that TKT was significantly up-regulated in cervical cancer tissues compared to normal controls. Gain-of-function and loss-of-function studies showed that the miR-497/TKT axis was a critical modulator in DDP chemosensitivity as demonstrated by cell viability and apoptosis assays. Mechanistically, DDP chemosensitivity induced by the miR-497/TKT axis was associated with glutathione (GSH) depletion and reactive oxygen species (ROS) generation, and GSH treatment effectively abrogated miR-497/TKT-mediated chemosensitivity. In conclusion, these findings suggest that a deregulated miR-497/TKT axis has important implications in the cervical cancer cellular response to DDP, and thus targeting this axis may be a promising way to improve chemosensitivity in cervical cancer.
ABSTRACT
MicroRNAs (miRNA) play crucial roles in regulating cell proliferation, differentiation and developmental timing. Aberrantly expressed miRNAs have recently emerged as key regulators of metabolism. However, little is known about its role in tumor metabolism of cervical cancer. In this study, we determined the oncogenic effects of miRNAs on Warburg effect, a metabolic phenotype that allows cancer cells to utilize glucose even under aerobic conditions. A gain-of-function study was performed in 12 down-regulated miRNAs that frequently reported in cervical cancer. We found that miR-34a plays a suppressive role in Warburg effect as evidenced by decreased lactate production and glucose consumption. Knockdown of oncoprotein E6 expression of human papillomavirus in SiHa and HeLa cells by siRNAs lead to an increased protein level of p53, decreased level of miR-34a, as well as reduced Warburg effect. Subsequently, lactate dehydrogenase A (LDHA), which catalyzes the last key step in glycolysis, was identified as a direct target of miR-34a. Silencing of LDHA or introduction of miR-34a significantly attenuated colony formation ability and invasive capacity of SiHa and HeLa cells, and these effects were fully compromised by reintroduction of LDHA. In conclusion, our findings demonstrated that deregulated miR-34a/LDHA axis induced by HPV E6/p53 signaling facilitates tumor growth and invasion through regulating Warburg effect in cervical cancer, and provided new insights into the mechanism by which miR-34a contributes to the development and progression of cervical cancer.
ABSTRACT
BACKGROUND: Infection with hepatitis B virus (HBV) during pregnancy may lead to perinatal transmission. OBJECTIVES: To compare the efficacy and safety of telbivudine versus lamivudine in interrupting perinatal transmission of hepatitis B virus. STUDY DESIGN: All pregnant women enrolled in this study were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Test patients underwent antiviral therapy with telbivudine or lamivudine while control patients received hepatitis B immune globulin (HBIG) injection. RESULTS: Patients in the telbivudine group had significantly lower HBV DNA and HBeAg levels and higher HBV DNA negative conversion rates compared to those in the lamivudine group before delivery. HBV DNA negative conversion rates in patients with abnormal alanine aminotransferase (ALT) levels were significantly higher than those in patients with normal ALT levels in the telbivudine and lamivudine groups before delivery. The intrauterine HBV infection rate and the percentage of immunization failure were both 0% in the telbivudine and lamivudine groups (χ(2)=0, 0; P=1, 1 respectively), compared to both 5% in the HBIG group (χ(2)=11.83, 7.86; P=0.002, 0.009 respectively). The side effects of three groups in mother and child were all unobvious. CONCLUSIONS: Telbivudine and lamivudine can reduce HBV DNA levels in pregnant women, interrupt the vertical transmission of HBV and be used safely in mothers and children.
