microRNAs (miRNAs) are short non-coding RNA molecules which are involved in the regulation of various biological processes. Drug resistance has become a major obstacle to successful chemotherapy of ovarian cancer. The aim of this study was to investigate microRNA expression profiles in cisplatin-resistant ovarian cancer cells and the role of miR-130a in regulating drug resistance. Analysis of differentially expressed miRNAs between SKOV3 and SKOV3/CIS cells was assessed by miRNA microarrays. Target prediction of miRNAs was determined with the help of PicTar or TargetScan. Among these miRNAs, the expression of miR‑130a was verified using qRT-PCR. The expression of MDR1 mRNA and P-glycoprotein (P-gp) after cellular transfection was examined using qRT-PCR and western blotting, respectively. Cisplatin sensitivity was detected by the MTT assay. We indentified 35 downregulated and 54 upregulated miRNAs in SKOV3/CIS compared to those in SKOV3. We found that miR-130a was upregulated in SKOV3/CIS compared to the parental SKOV3 cells, and PTEN was predicted to be the potential target of miR-130a. Moreover, downregulation of miR-130a could inhibit MDR1 mRNA and P-gp expression and overcome the cisplatin resistance in SKOV3/CIS cells, which indicated that miR-130a may be associated with MDR1/P-gp-mediated drug resistance and plays the role of an intermediate in drug-resistance pathways of PI3K/Akt/PTEN/mTOR and ABC superfamily drug transporters in SKOV3/CIS cells. This study provides important information for the development of targeted gene therapy for reversing cisplatin resistance in ovarian cancer.
Chemoresistance remains a major obstacle to effective treatment in patients with ovarian cancer, and recently increasing evidences suggest that miRNAs are involved in drug-resistance. In this study, we investigated the role of miRNAs in regulating cisplatin resistance in ovarian cancer cell line and analyzed their possible mechanisms. We profiled miRNAs differentially expressed in cisplatin-resistant human ovarian cancer cell line A2780/DDP compared with parental A2780 cells using microarray. Four abnormally expressed miRNAs were selected (miR-146a,-130a, -374a and miR-182) for further studies. Their expression were verified by qRT-PCR. MiRNA mimics or inhibitor were transfected into A2780 and A2780/DDP cells and then drug sensitivity was analyzed by MTS array. RT-PCR and Western blot were carried out to examine the alteration of MDR1, PTEN gene expression. A total of 32 miRNAs were found to be differentially expressed in A2780/DDP cells. Among them, miR-146a was down-regulated and miR-130a,-374a,-182 were upregulated in A2780/DDP cells, which was verified by RT-PCR. MiR-130a and miR-374a mimics decreased the sensitivity of A2780 cells to cisplatin, reversely, their inhibitors could resensitize A2780/DDP cells. Furthermore, overexpression of miR-130a could increase the MDR1 mRNA and P-gp levels in A2780 and A2780/DDP cells, whereas knockdown of miR-130a could inhibit MDR1 gene expression and upregulate the PTEN protein expression .In a conclusion, the deregulation of miR-374a and miR-130a may be involved in the development and regulation of cisplatin resistance in ovarian cancer cells. This role of miR-130a may be achieved by regulating the MDR1 and PTEN gene expression.
ObjectiveTo analyze the clinic-pathological characteristics of women with cervical cancers in southwestern China and discuss the features and prognosis of young patients.MethodsA retrospective study was performed, which consisted of 1,543 patients diagnosed with cervical cancer and underwent treatment at West China Second University Hospital between November 2005 and December 2010. Among them, 154 young patients with surgical procedures between November 2005 and December 2008 were selected for a 5-year follow-up and prognostic analysis.ResultsThe proportion of advanced FIGO stage in patients aged over 35 years was higher than in patients aged 35 years or younger (55.1% vs 38.8%, P<0.001), and strong correlation was found between FIGO stages and the postoperative pathological risk factors (P<0.05). 312 patients (20.2%) were under 35 years old in the last 5 years. The proportion of cervical adenocarcinoma remained high in young patients (13.6%), and young women with adenocarcinoma had a higher rate of LN metastases, comparing with those with squamous cell carcinoma (42.9% vs 15.8%, P = 0.004). Young patients with adenocarcinoma had shorter progression-free survival than those who had squamous cell carcinoma (P = 0.024). Patients aged 35 years or younger with positive postoperative pathological risk factors had shorter progression-free survival, comparing with those with negative factors (P<0.01).ConclusionPatients over 35 years were preliminarily diagnosed as advanced FIGO stage and they were more likely to have deep stromal invasion, LVSI, LN metastases, parametrial and surgical margin involvement. Regarding to young patients, cervical adenocarcinoma increased the risk of LN metastases and positive postoperative pathological risk factors could apparently worsen the prognosis. Histological type and LN metastases were independent prognostic factors for young patients in southwestern China. We re-emphasize the importance of health education and regular smear screening for elder women, and more attention should be paid to young patients with adenocarcinoma or LN metastases.
Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer, which exhibits invasive traits. MicroRNAs (miRNAs/miRs) have been demonstrated to serve important functions in the pathogenesis of EOC. However, the function of miR-545 in EOC remains unknown. In the present study, the function of miR-545 in EOC was analyzed and it was identified that miR-545 is downregulated in EOC tissues and cell lines. Additionally, a low level of miR-545 expression was associated with a low survival rate of patients with EOC. Furthermore, overexpression of miR-545 inhibited cell growth and promoted apoptosis. Suppression of miR-545 promoted cell growth and inhibited apoptosis. Additionally, the RAC-γ serine/threonine-protein kinase gene was targeted by miR-545. Thus, it may be concluded that miR-545 exhibited antitumor traits in EOC.
The aim of the present study was to discuss the clinicopathological characteristics of endometrial carcinoma in young females with polycystic ovary syndrome (PCOS), and to review the current literature. A total of 9 patients with histopathologically confirmed endometrial cancer in young females with PCOS at the West China Second Hospital of Sichuan University between December 2007 and September 2013 were included. The clinicopathological characteristics of the patients were analyzed. The age range of the patients was 24-38 years (median age, 29), all of the cases had abnormal vaginal bleeding and endometrioid adenocarcinoma was the most common histopathological subtype observed (8 cases, 88.9%). Of the patients, 2 had well-differentiated cases and 7 patients had moderately differentiated cases. None of the patients received regular PCOS treatments and did not turn up for regular checkups before they were diagnosed with endometrial carcinoma. Additionally, 7 patients received staging laparotomy with a total abdominal hysterectomy and bilateral salpingo-oophorectomy, 1 patient underwent an endometrial resection under hysteroscopy and the final patient received a high-dose of medroxyprogesterone treatment without surgery. In conclusion, doctors should take into consideration that young women with PCOS may also exhibit an endometrial carcinoma, and diagnosing and treating the endometrial carcinoma as early as possible in the young patients with PCOS is necessary.
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