ABSTRACT
BACKGROUND: Hsa-mir-92a acts as an onco-miRNA and may contribute to the progression and invasion of cervical cancer, which is a common malignant tumor in women worldwide. The objective of the present study was to evaluate whether serum hsa-mir-92a could serve as a diagnostic biomarker for cervical cancer patients. METHODS: The expression levels of hsa-mir-92a were analyzed in the serum of patients with CIN I, CIN II, CIN III, cervical cancer Ia - IIa and compared with those of the control group samples. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic significance of cervical cancer. RESULTS: It was found that the expression of hsa-miR-92a in the serum of individuals with CIN or cervical cancer was significantly higher than that in healthy volunteers (p < 0.01). The expression of hsa-miR-92a was higher in the serum of patients with advanced stage and cervical cancer than those with early stage. ROC analysis revealed that the cutoff value of hsa-mir-92a was 1.52 for the diagnosis of CIN and cervical cancer. The sensitivity and specificity were 69.6% and 80.4%, respectively, and an area under the curve (AUC) was 0.83. CONCLUSIONS: hsa-mir-92a up-regulation was associated with cervical cancer and the serum level of hsa-mir-92a could be used as an independent marker for the diagnosis of cervical cancer.
Subject(s)
Biomarkers, Tumor/blood , Circulating MicroRNA/blood , MicroRNAs/blood , Real-Time Polymerase Chain Reaction , Uterine Cervical Dysplasia/blood , Uterine Cervical Neoplasms/blood , Adult , Area Under Curve , Biomarkers, Tumor/genetics , Case-Control Studies , Circulating MicroRNA/genetics , Female , Humans , MicroRNAs/genetics , Middle Aged , Neoplasm Staging , Predictive Value of Tests , ROC Curve , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Young Adult , Uterine Cervical Dysplasia/genetics , Uterine Cervical Dysplasia/pathologyABSTRACT
MyD88 was reported to be associated with paclitaxel sensitivity in lung cancer; however, its roles in breast cancer remain unclear. The objective of this study is to investigate the expression and function of MyD88 in breast cancer. Immunohistochemistry (IHC) was used to analyze the expression of MyD88 in both breast cancer tissues and adjacent normal tissues. Real-time PCR and Western blots were further used to measure the messenger RNA (mRNA) and protein expression. The proliferation was assessed by WST-1. Flow cytometry was used to measure the cell cycle and apoptosis. The transwell assay was used to observe the change of migration and invasion of transfected cells. In breast cancer tissues, the expression of MyD88 was significantly higher than that in tumor-adjacent normal tissues (P < 0.001). MyD88 expression was found to be associated with the differentiation stages (P = 0.019). Kaplan-Meier survival curves showed statistically significant difference on survival in patients with high expression of MyD88 compared with those with normal expression of MyD88 (P = 0.018). Knockdown of MyD88 reduced the proliferation, migration, and invasion of MCF-7 cells and increased the sensitivity of MCF-7 cells to paclitaxel treatment through the inhibition of activation of NF-κB via PI3K/Akt. Our data indicate that MyD88 may be a potential target molecule to be used in diagnosis and treatment of breast cancer.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Breast Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , Gene Expression , Myeloid Differentiation Factor 88/genetics , Paclitaxel/pharmacology , Adult , Aged , Aged, 80 and over , Animals , Apoptosis/drug effects , Biomarkers, Tumor , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Female , Gene Knockdown Techniques , Humans , Mice , Middle Aged , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/metabolism , Neoplasm Grading , Neoplasm Staging , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: The low effectiveness of anticancer drugs remains a major unresolved obstacle to successful chemotherapy. Recently, much evidence on the roles of miRNAs in determining drug-sensitivity/resistance has been emerging. The relationship between miRNA-149 expression and paclitaxel chemoresistance in human ovarian cancer cells remains largely unknown. METHODS: This study investigated the relationship between miRNA-149 expression and the sensitivity of ovarian cancer A2780 cells to paclitaxel treatment. To achieve the down-regulation of miRNA-149 gene expression in A2780 cell line, the cells were infected with lentivirus carrying inhibitor of miRNA-149. Western blot and qRT-PCR were used to detect relevant protein levels and the expressions of mRNAs of interest. Cell proliferation was measured by CCK-8 assay. Flow cytometry was used to measure cell cycle and apoptosis. Transwell migration assay was used to observe the change of migration of transfected cells. RESULTS: Down-regulation of miRNA-149 decreased the sensitivity of ovarian cancer A2780 cells to paclitaxel. After paclitaxel treatment, decreased apoptosis and G2 phase ratio, increased cell migration, increased level of Bcl-2, and decreased level of Bax were found in miRNA-149-down-regulated A2780 cells. MiRNA-149 down-regulation resulted in increased expression of MyD88 in A2780 cells. Down-regulation of miRNA-149 in A2780 cells increased MyD88 expression and decreased their sensitivity to paclitaxel treatment. CONCLUSION: Our findings suggest that miRNA-149 mediates the susceptibility of paclitaxel by regulating MyD88 expression in ovarian cancer cells.
Subject(s)
Drug Resistance, Neoplasm/genetics , MicroRNAs/biosynthesis , Myeloid Differentiation Factor 88/biosynthesis , Ovarian Neoplasms/genetics , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , MicroRNAs/genetics , Myeloid Differentiation Factor 88/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , RNA, Messenger/biosynthesisABSTRACT
Ursolic acid (UA), a potential chemotherapeutic agent, has the properties of inhibition of the growth of many human cancer cell lines. Whether UA can inhibit the growth and metastasis of human gastric cancer cells remains unknown. In this study, it was found that UA inhibited the growth and metastasis of human gastric cancer cells in vitro. Our results showed the increase of the percent of apoptotic cells and G1 phase, the inhibition of cell migrations well as the decrease of the expression of Bax, caspase 3 and Bcl-2 in BGC-823 cells after the treatment with UA. Real-time quantitative PCR analysis showed that UA treatment upregulated the level of miR-133a in BGC-823 cells. Overexpression of miR-133a increased the G1 phase of cell cycle and decreased Akt1 expression in BGC-823 cells. These outcomes might be secondary to the increased expression of miR-133a after the treatment with UA.