Background: Cisplatin resistance (DDP-resistance) remains one of the major causes of poor prognosis in females with ovarian cancer. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of cellular processes, including chemoresistance. The aim of this study was to explore the role of HOX transcript antisense RNA (HOTAIR) in DDP-resistant ovarian cancer cells. Methods: DDP-resistant ovarian cancer cell lines (SKOV3/DDP and A2780/DDP) were established. Real-time PCR, western blot, dual-luciferase reporter assay, and flow cytometry were then used to evaluate the effect of HOTAIR/miR-138-5p axis on chemoresistance of DDP-resistant ovarian cancer cells to DDP. Results: We found that HOTAIR was upregulated in DDP-resistant cells, while miR-138-5p was downregulated. Knockdown of HOTAIR increased the expression of miR-138-5p in DDP-resistant cells and miR-138-5p is directly bound to HOTAIR. Upregulation of miR-138-5p induced by HOTAIR siRNA or by its mimics enhanced the chemosensitivity of DDP-resistant cells and decreased the expression of EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) and SIRT1 (sirtuin 1). Furthermore, the HOTAIR silencing-induced chemosensitivity of DDP-resistant cells was weakened by miR-138-5p inhibitor. Conclusions: These data demonstrate that HOTAIR acts as a sponge of miR-138-5p to prevent its binding to EZH2 and SIRT1, thereby promoting DDP-resistance of ovarian cancer cells. Our work will shed light on the development of therapeutic strategies for ovarian cancer treatment.
Abstract.Observational and experimental studies have produced inconsistent evidence about the association of serum levels of B-type natriuretic peptide (BNP) with anthracycline-induced cardiotoxicity (AIC). Therefore, the current meta-analysis examined the association between serum BNP levels and AIC by using data from high quality studies published in peer-reviewed journals. Relevant studies were identified through literature searches of China National Knowledge Infrastructure (CNKI), Web of Science, PubMed, Google Scolar and China BioMedicine (CBM). STATA software was used in this meta-analysis for statistical analysis. In addition, the crude standardized mean difference (SMD) with 95% confidence interval (CI) for the highest vs. the lowest category of serum BNP levels was calculated. A total of 8 independent case-control studies, containing 126 AIC patients and 569 healthy controls, were included for the current meta-analysis. The results indicated a significant difference in serum BNP levels between the cardiotoxic group and normal group, with respect to post-treatment and pretreatment with anthracyclines. Specifically, the serum levels of BNP increased remarkably after treatment with anthracyclines in the cardiotoxic group, compared with the normal group. No publication bias was detected in this meta-analysis. The findings of the present study provide strong evidence that serum BNP levels may be associated with AIC.
Background: The acetabular index (AI) is the most commonly used parameter for diagnosing hip dysplasia. Pelvic malposition can result in misinterpretation of AI measurement especially in younger children. We aimed to investigate the correlation between pelvic orientation and acetabular index (AI) by using digital reconstructed radiographs (DRRs) and identify reliable parameters predictive of pelvic orientation on plain radiographs. Methods: We retrospectively identified 33 children (52 hips) who received dual source CT examinations. Virtual pelvic models were reconstructed after scanning. After orientating in the standard neutral position, the models were rotated and tilted around corresponding axes. DRRs were generated at every 3°during the process. The acetabular index, the horizontal diameter (Dh) and vertical diameter (Dv) of bilateral obturator foramina, the vertical distance (h) between upper border of pubic symphysis, and Hilgenreiner's line were measured on each DRR by two independent observers. Rotation index (Rr = right Dh/left Dh), tilt index (Rt = h/Dv), intra-observer error, and interobserver error of AI were calculated. Results: For tilt and rotation up to 12.0°, AI increased with anterior tilt and decreased with posterior tilt. And for rotation, it increased on the side toward which the pelvis rotated and decreased on the opposite side. AI varied dramatically if angulation exceeded 6.0°. Malposition below this limit demonstrated the intra-and inter-observer errors were ± 2.0°and ± 3.0°respectively and caused no significant effect on AI measurement. Conclusions: For children up to age 6 years, an acceptable pelvic plain radiograph can be determined when Rt is approximately between 0.9 and 1.4 and Rr between 0.7 and 1.5. For the first time, we have identified parameters derived from a group of subjects which can predict this degree of malposition. The parameters obturator diameters (Dh), obturator height (Dv), and distance (h) between symphysis and Hilgengreiner's line can be feasibly measured on X-ray and employed in clinical practice to assess the acceptability of the pediatric pelvic radiograph prior to measurement of the AI.
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