Human growth factor receptor-bound protein-7 (GRB7) is a pivotal mediator involved in receptor tyrosine kinase signaling and governing diverse cellular processes. Aberrant upregulation of GRB7 is frequently associated with the progression of human cancers. However, the molecular mechanisms leading to the upregulation of GRB7 remain largely unknown. Here, we propose that the epigenetic modification of GRB7 at the post-transcriptional level may be a crucial factor leading to GRB7 upregulation in ovarian cancers. Methods: The upstream miRNA regulators were predicted by in silico analysis. Expression of GRB7 was examined by qPCR, immunoblotting and immunohistochemical analyses, while miR-193a-3p levels were evaluated by qPCR and in situ hybridization in ovarian cancer cell lines and clinical tissue arrays. MS-PCR and pyrosequencing analyses were used to assess the methylation status of miR-193a-3p. Stable overexpression or gene knockdown and Tet-on inducible approaches, in combination with in vitro and in vivo tumorigenic assays, were employed to investigate the functions of GRB7 and miR-193a-3p in ovarian cancer cells. Results: Both miR-193a-3p and its isoform, miR-193b-3p, directly targeted the 3' UTR of GRB7. However, only miR-193a-3p showed a significantly inverse correlation with GRB7-upregulated ovarian cancers. Epigenetic studies revealed that methylation-mediated silencing of miR-193a-3p led to a stepwise decrease in miR-193a-3p expression from low to high-grade ovarian cancers. Intriguingly, miR-193a-3p not only modulated GRB7 but also ERBB4, SOS2 and KRAS in the MAPK/ERK signaling pathway to enhance the oncogenic properties of ovarian cancer cells in vitro and in vivo. Conclusion: These findings suggest that epigenetic silencing of miR-193a-3p by DNA hypermethylation is a dynamic process in ovarian cancer progression, and miR-193a-3p may be explored as a promising miRNA replacement therapy in this disease.

OBJECTIVE. To evaluate the prevalence of dysmenorrhoea, its impact, and management approaches in Hong Kong university students, and to compare between medical and non-medical students for any potential differences in coping strategies. DESIGN. Cross-sectional questionnaire survey. SETTING. The University of Hong Kong, Hong Kong. PARTICIPANTS. A total of 240 undergraduate (128 medical and 112 non-medical) students. MAIN OUTCOME MEASURES. Data on the presence and severity of dysmenorrhoea, its impact on daily life, management approaches, specific strategies, and their self-perceived effectiveness were obtained and analysed. RESULTS. In these subjects, the prevalence of dysmenorrhoea was 80% (95% confidence interval, 75-85%) with a mean (standard deviation) pain score of 5.0 (1.7). The most common impacts on daily life included reduced ability to concentrate and/or disturbance with study (75%) and changes in normal physical activity (60%). Only 6% sought medical advice, while 70% practised self-management. Pain scores and pain affecting normal physical activities were important predictive factors for self-management and for management based on pharmacological or non-pharmacological means. The commonest specific strategies used were a warm beverage (62%), paracetamol (57%), and sleeping (45%), while the most effective strategies were non-steroidal anti-inflammatory drugs (100%), traditional Chinese medicine (93%), and dietary/nutritional supplements (92%). Regarding the comparison of medical and non-medical students, the former used fewer pharmacological strategies among the various management approaches investigated. CONCLUSION. With data showing dysmenorrhoea as a very common condition having a significant impact in the Hong Kong community, primary care doctors should reassure young women with dysmenorrhoea that it is a common experience in the same age-group. Health education on the existence of effective treatment from medical practitioners could help women whose dysmenorrhoea was not controlled by self-management.

Intraperitoneal metastasis is a common occurrence and is usually involved in the poor prognosis of ovarian cancer. Its specific metastatic pattern implies that certain indispensable microenvironmental factors secreted in the peritoneal cavity can direct metastatic ovarian cancer cells to permissive niches for secondary lesion formation. However, the underlying molecular mechanisms are ill defined. Herein, we report that GRO-α and IL-8 are predominately upregulated in culture media derived from either normal or cancerous omenta and are associated with increased ovarian cancer aggressiveness.