miRNAs have the potential to act on diverse downstream genes, and miRNA signatures of HPV-infected tissues may provide insight into HPV-related carcinogenesis. We set out to profile miRNA expression in HPV-infected samples and relate this to histological and grade-specific alterations in the spectrum of cervical carcinogenesis in vivo. A total of 31 miRNAs showed significant and continuous expression along with the progression from normal cervical tissue to cancer, and six of them were validated in 133 samples. By bioinformatics analyses, we established a putative HPV-associated miRNA-mRNA regulatory network, showing that miR-29 is the most highly enriched. We also found that YY1 and CDK6 were both positively correlated with E6/E7 RNA expression and targeted by tumour-suppressive miR-29. Evidence of miR-29 involvement in HPV infection was further verified in patient samples and by various experimental approaches. Taken together, our results suggest that HPVs have oncogenic properties at least in part by reshaping the milieu of cellular miRNAs. miR-29 restrains cell cycle progression and induces apoptosis via YY1 and CDK6 promoting malignant transformation induced by HPV, although the abnormality of miR-29 in HPV-infected cells might be regulated in an indirect way.

Pelvic lymph node metastases are regarded as the most important risk factor and a predictor of poor prognosis for patients with cervical cancer. Exploration of metastasis-related molecules is helpful toward improving the prognosis in cervical cancer. To identify the role of miR-375 in metastasis and progression of cervical cancer, we examined the expression of miR-375 in 170 cervical cancer tissues and 68 normal cervical tissues, using stem-loop quantitative PCR, and found that the expression of miR-375 in cervical cancer tissues was significantly decreased by 4.45-fold, compared with 68 normal tissues. A significant correlation existed between miR-375 expression and clinicopathologic parameters, including lymph node metastasis of cervical cancer. Overexpressed miR-375 suppressed cell proliferation, blocked G1-to-S cell-cycle transition, and inhibited cell migration and invasion in human cervical SiHa and CaSki cells. SP1, a potential target gene of miR-375, was inversely correlated with miR-375 expression in cervical cancer tissues. Moreover, SP1 was negatively regulated by miR-375, and knockdown of SP1 by siRNA inhibited cell malignant behaviors. Thus, our findings suggest that down-regulated miR-375 promotes cell malignant behaviors via the target gene SP1 and may consequently contribute to the progression of cervical cancer.

Echo-planar imaging (EPI) is very sensitive to patient-induced field inhomogeneity caused by susceptibility changes between different anatomical regions. This results in geometric and intensity distortions in the image, especially near tissue/air and tissue/bone interfaces. A new approach is presented to reduce geometric and intensity distortions in EPI. A phase-encoded multireference scan is used to estimate the amplitude and phase errors in the measured signals due to the field inhomogeneity. The EPI data is corrected using both the amplitude and phase of the measured errors. This technique has been evaluated using EPI pulse sequences implemented with conventional gradients and implemented with imaging systems that have special resonating gradients and fast analog to digital converters. The results in both phantom and human studies show that in the absence of object motion the new correction technique can effectively reduce the geometric and intensity distortions.

No abstract

No abstract

In this study, we developed an autodetection technique for the equatorial plasma depletions (EPDs) and their occurrence and depletion amplitudes based on in situ electron density measurements gathered by Swarm A satellite. For the first time, comparisons are made among the detected EPDs and their amplitudes with the loss of Global Positioning System (GPS) signal of receivers onboard Swarm A, and the Swarm Level‐2 product, Ionospheric Bubble Index (IBI). It has been found that the highest rate of EPD occurrence takes place generally between 2200 and 0000 magnetic local time (MLT), in agreement with the IBI. However, the largest amplitudes of EPD are detected earlier at about 1900–2100 MLT. This coincides with the moment of higher background electron density and the largest occurrence of GPS signal loss. From a longitudinal perspective, the higher depletion amplitude is always witnessed in spatial bins with higher background electron density. At most longitudes, the occurrence rate of postmidnight EPDs is reduced compared to premidnight ones; while more postmidnight EPDs are observed at African longitudes. CHAMP observations confirm this point regardless of high or low solar activity condition. Further by comparing with previous studies and the plasma vertical drift velocity from ROCSAT‐1, we suggest that while the F region vertical plasma drift plays a key role in dominating the occurrence of EPDs during premidnight hours, the postmidnight EPDs are the combined results from the continuing of former EPDs and newborn EPDs, especially during June solstice. And these newborn EPDs during postmidnight hours seem to be less related to the plasma vertical drift.

Quantitative real-time RT-PCR (RT-qPCR) is being widely used in microRNA expression research. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in microRNA RT-qPCR studies. The aim of this study was to identify the most stable reference gene(s) for quantification of microRNA expression analysis in uterine cervical tissues. A microarray was performed on 6 pairs of uterine cervical tissues to identify the candidate reference genes. The stability of candidate reference genes was assessed by RT-qPCR in 23 pairs of uterine cervical tissues. The identified most stable reference genes were further validated in other cohort of 108 clinical uterine cervical samples: (HR-HPV-normal, n = 21; HR-HPV+ normal, n = 19; cervical intraepithelial neoplasia [CIN], n = 47; cancer, n = 21), and the effects of normalizers on the relative quantity of target miR-424 were assessed. In the array experiment, miR-26a, miR-23a, miR-200c, let-7a, and miR-1979 were identified as candidate reference genes for subsequent validation. MiR-23a was identified as the most reliable reference gene followed by miR-191.The use of miR-23a and miR-191 to normalize expression data enabled detection of a significant deregulation of miR-424 between normal, CIN and cancer tissue. Our results suggested that miR-23a and miR-191 are the optimal reference microRNAs that can be used for normalization in profiling studies of cervical tissues; miR-23a is a novel microRNA normalizer.

No abstract