ABSTRACT
Background: MicroRNAs (miRNAs) are non-coding small RNAs that function as negative regulators of gene expression and are involved in tumour biology. The eIF4E-binding proteins (eIF4EBPs) play essential roles in preventing translation initiation and inhibiting protein synthesis at a global or message-specific level in a variety of tumours. Methods: According to comparative miRNA profiles of clinical cervical cancer and non-cancerous cervical tissue specimens, several miRNAs were aberrantly expressed in the cervical cancer samples. C33a and SiHa cell proliferation and apoptosis were detected using methyl thiazolyl tetrazolium (MTT) and flow cytometry assays, respectively. Results: Among the aberrantly expressed miRNAs, miR-22-3p was significantly differentially expressed in cervical cancer tissues and was highly associated with cervical cancer cell growth regulation. In addition, bioinformatic predictions and experimental validation were used to identify whether eIF4E-binding protein 3 (eIF4EBP3) was a direct target of miR-22-3p; eIF4EBP3 protein levels were generally low in the cervical cancer tissues. Furthermore, functional studies revealed that either a miR-22-3p inhibitor or eIF4EBP3 overexpression could induce apoptosis in cervical cancer cells in vitro. Importantly, we found that eIF4EBP3 accumulation could significantly attenuate cervical cancer cell proliferation triggered by a miR-22-3p mimic as well as enhance apoptosis in cervical cancer cells. Conclusion: Taken together, our data provide primary proof that miR-22-3p can induce cervical cancer cell growth at least in part by up-regulating its expression to decrease eIF4EBP3 expression levels; miR-22-3p thus holds promise as a prognostic biomarker and potential therapeutic target for treating cervical cancer.
Subject(s)
Carcinoma, Squamous Cell/pathology , Carrier Proteins/genetics , MicroRNAs/genetics , Uterine Cervical Neoplasms/pathology , Adult , Apoptosis/genetics , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Middle Aged , Uterine Cervical Neoplasms/geneticsABSTRACT
As a mitochondrial membrane protein, globular C1q receptor (gC1qR) can mediate a variety of biological responses. Our study aims to investigate the role of gC1qR in paclitaxel-induced apoptosis of human ovarian cancer cells and to elucidate its potential molecular mechanism. The level of gC1qR was examined using real-time PCR and western blot analyses. Human ovarian cancer cells viability, migration, and proliferation were detected using the water-soluble tetrazolium salt (WST-1) assay, the transwell assay, and H-thymidine incorporation into DNA (H-TdR) assay, respectively. Apoptosis in cells was assessed using flow cytometric analysis. The intracellular reactive oxygen species was estimated by the fluorescence of H2DCFDA and the mitochondrial membrane potential was tested using a JC-1 probe. The expression of the gC1qR gene decreased significantly in human ovarian cancer tissues relative to the surrounding non-neoplastic ovarian tissues. Cells treated with paclitaxel showed increased gC1qR gene expression, cell apoptosis, and mitochondria dysfunction, and the effects on these cells could be abrogated by the addition of gC1qR small-interfering RNA or α-lipoic acid that was used to protect the mitochondria function. In summary, these data support a mechanism that gC1qR-induced mitochondria dysfunction was involved in the paclitaxel-mediated apoptosis of ovarian cancer cells.
ABSTRACT
This study assessed the growth trends and reference ranges of the ultrasound parameters, fetal abdominal subcutaneous tissue thickness (ASTT) and subscapular subcutaneous tissue thickness (SSTT), in the last two trimesters of normal pregnancy in a Chinese population. We recruited 744 healthy women with singleton pregnancies. The ASTT and SSTT were evaluated at different times between 21 and 36 weeks of gestation. The correlations between these parameters and fetal gestational weeks were assessed using linear regression analysis. Both ASTT and SSTT increased with gestation, and both parameters showed a strong correlation with gestation (ASTT vs. GA, R(2)â= 0.792; P<0.0001; SSTT vs. GA, R(2)â= 0.302; P<0.0001). Time-specific reference ranges, including 5th, 50th and 95th percentiles and means ± SD, were constructed for ASTT and SSTT. These results provide a preliminary reference range to evaluate whether fetal development and maternal metabolic health is normal or not in a Chinese population.