The role of p53-microRNA 200-Moesin axis in invasion and drug resistance of breast cancer cells.

This study aimed to analyze the expression of microRNAs in relation to p53 status in breast cancer cells and to delineate the role of Moesin in this axis. We used three isogenic breast carcinoma cell lines MCF7 (with wild-type p53), 1001 (MCF7 with mutated p53), and MCF7-E6 (MCF7 in which p53 function was disrupted). MicroRNA expression was analyzed using microarray analysis and confirmed by real-time polymerase chain reaction. The 1001 clone with mutant p53 showed 22 upregulated and 25 downregulated microRNAs. The predicted targets of these 47 microRNAs were >700 human genes belonging to interesting functional groups such as stem cell development and maintenance. The most significantly downregulated microRNAs in the p53-mutant cell line were from the miR-200 family. We focused on miR-200c which targets many transcripts involved in epithelial-to-mesenchymal transition including Moesin. We found that Moesin was expressed in 1001 but not in its p53 wild-type parental MCF7 consistent with the observed mesenchymal features in the 1001, such as vimentin positivity, E-cadherin negativity, and ZEB1 positivity in addition to the morphological changes. After Moesin silencing, the p53-mutant cells 1001 reverted from mesenchymal-to-epithelial phenotype and showed subtle reduction in migration and invasion and loss of ZEB1 and SNAIL expression. Interestingly, Moesin silencing restored the 1001 sensitivity to Doxorubicin. These results indicate that loss of miR-200c, as a consequence of p53 mutation, can upregulate Moesin oncogene and thus promote carcinogenesis. Moesin may play a role in metastasis and drug resistance of breast cancer.

Prevalence and clinicopathological characteristics of appendiceal carcinoids in Sharjah (United Arab Emirates).

AIM: To determine the incidence and clinico-pathological profile of appendiceal carcinoids in a cohort of patients undergoing emergency appendicectomies for clinically suspected acute appendicitis in Sharjah, United Arab Emirates (UAE). METHODS: The study included the retrospective data of 964 patients operated for clinically suspected acute appendicitis, and the resected specimens were received at Al-Qasmi Hospital (Sharjah) from January 2010 to December 2010. The data of the patients who were histologically reported to have carcinoid tumors of the appendix were extensively evaluated for the patient's demographics, indication for surgery, surgical procedure, tumor localization in the appendix, diameter of the lesion, concomitant appendicitis, immunohistochemistry studies and clinical follow-up. RESULTS: Out of the 964 patients included in the study, 9 (0.93%) were found to have appendiceal carcinoids. The mean age reported was 28.7 years with a male to female ratio of 2:1. Eight tumors were located near the tip of the appendix with a mean diameter of 3.3 mm, while the remaining one was near the proximal end of the appendix. All the cases were associated with concomitant suppurative appendicitis. In seven reported cases, tumors were confined to the muscular layer while in one case each there was an extension to the serosa and mesoappendix, respectively. All tumors were found to be positive for chromogranin A, synaptophysin and neuron-specific enolase on immunohistochemistry but negative for cytokeratin-7. None of the patients developed recurrence or any reportable complications in the short follow-up period (12-26 mo) that was arranged as a six-monthly re-evaluation by abdominal ultrasonography. CONCLUSION: Our study found a higher incidence of appendiceal carcinoids in patients undergoing emergency appendectomy for acute appendicitis in Sharjah, UAE compared to two previous studies from the Persian Gulf region. Interestingly, tumors were found to be more commonly in young males, which is in contrast to previous studies. Moreover, all the tumors were positive for common neuroendocrine markers.