caffeic acid Depending on the target gene KLF may
Depending on the target gene, KLF4 may function as both a repressor and activator of transcription [31,32]. Previous studies demonstrated Bax could be a tumor-suppressor target of KLF4 functioning as an anti-oncogene [33,34]. When transfected with anti-miR-367, MG-63 and U2OS caffeic acid showed enhanced sensitivity to ADR, with up-regulation of KLF4, Bax and activation of caspase-3, which were also negatively regulated by miR-367 overexpression. These data suggested that ADR induced apoptosis in OS cells through the regulation of KLF4 via miR-367, then the pro-apoptosis factor Bax and cleavage of caspase-3 could lead to final apoptosis.
In summary, our data demonstrates that miR-367 functions as an oncogene in OS targeting the tumor suppressor KLF4; ADR induces apoptosis in MG-63 and U2OS via the regulation of miR-367/KLF4/Bax signaling pathway; miR-367 enhances the chemotherapy resistance of ADR to OS cells through suppressing KLF4. Our data shows that miR-367 could be a potential biomarker of chemotherapy resistance and therapeutic target against OS.
Acknowledgments The authors are grateful to the American Journal Experts for helpful suggestion and highly qualified English language edit. This work was supported by grants from the National Natural Science Foundation of China (Nos. 81272942, 30973019 and 81202122) and Shanghai Science Foundation (No. 10411956000).
Introduction Over the last two decades, there has been a substantial increase in our understanding of the underlying biology of bone metastasis as well as the development and widespread incorporation of inhibitors of osteoclast function, namely bisphosphonates and denosumab, into clinical practice [1–3]. However, more recently there has been an international fall in peer-reviewed grant funding . This trend is also clearly evident in the declining grant support provided by the three Canadian federal funding agencies (Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC) and Social Sciences and Humanities Research Council (SSHRC) . This has led to increased challenges in performing academic bone metastasis research. The “Bone and the Oncologist New Updates” (BONUS) meeting is an annual Canadian multidisciplinary conference on the interaction of bone and cancer biology [5,6]. The focus of the 2015 BONUS Conference (16 and 17 April 2015) was to discuss potential key research themes that could form the basis for a coordinated national research strategy to tackle unmet clinical and research needs related to complications associated with cancer metastasis to bone.
Acknowledgements The BONUS meeting received an funding from Amgen Canada. This funding was used to organise the meeting. No speaker was paid. The sponsor has had no role in the preparation of this manuscript.
Introduction Breast cancer (BC) is the most common cancer in women, with approximately 1.7 million new diagnoses in 2012. This figure represents about 25% of all new cancer cases in women and 12% of those in the general population . Today, the median age at diagnosis is around 60 years and, since 20% of the global population will be aged >65 years by 2030, the number of women diagnosed with BC in this age group is likely to increase in the future. In women with BC, bone is the most common site of metastases [2–5]. Since bone lesions cause significant damage to the bone microstructure, patients with metastatic BC are at a high risk of skeletal-related events (SREs), such as bone pain, hypercalcemia, bone fracture, or spinal cord compression, which could potentially affect quality of life and life expectancy [6,7]. There are various bone metastasis treatments, depending on the number and the site of the lesions (i.e. radiotherapy, chemotherapy, or orthopedic intervention). Complementing these treatments is the role of bone-targeted agents such as bisphosphonates (BIS) [8,9]. Although no consensus has yet been reached on the optimal duration of BIS therapy, BIS use is generally recommended for a period of several years.