Publication

Silencing of CEBPB-AS1 modulates CEBPB expression and resensitizes BRAF-inhibitor resistant melanoma cells to vemurafenib

Rita Valador Fernandes
2020
Journal paper
Abstract

Introduction of targeted therapy in the treatment of metastatic cutaneous malignant melanoma (CMM) has improved clinical outcome during the last years. However, only in a subset of the CMM patients, this will lead to long-term effects. CEBPB is a transcription factor that has been implicated in various physiological and pathological processes, including cancer development. We have investigated its prognostic impact on CMM and unexpectedly found that higherCEBPBmRNA levels correlated with a longer overall survival. Furthermore, in a small cohort of patients with metastatic CMM treated with BRAF-inhibitors, higher levels ofCEBPBmRNA expression in the tumor cells prior treatment correlated to a longer progression-free survival. We have characterized an overlapping antisense transcript,CEBPB-AS1, with the aim to investigate the regulation of CEBPB expression in CMM and its impact on BRAF-inhibitor sensitivity. We demonstrated that silencing ofCEBPB-AS1resulted in epigenetic modifications in the CEBPB promoter and in increasedCEBPBmRNA and protein levels, inhibited proliferation and partially resensitized BRAF-inhibitor resistant CMM cells to this drug-induced apoptosis. Our data suggest that targetingCEBPB-AS1may represent a valuable tool to sensitize CMM cells to the BRAF-inhibitor-based therapies.

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Ontological neighbourhood
Related concepts (33)
Melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In women, they most commonly occur on the legs, while in men, they most commonly occur on the back. About 25% of melanomas develop from moles. Changes in a mole that can indicate melanoma include an increase in size, irregular edges, change in color, itchiness, or skin breakdown.
Treatment of cancer
Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy (including immunotherapy such as monoclonal antibody therapy) and synthetic lethality, most commonly as a series of separate treatments (e.g. chemotherapy before surgery). The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status). Cancer genome sequencing helps in determining which cancer the patient exactly has for determining the best therapy for the cancer.
Colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and fatigue. Most colorectal cancers are due to old age and lifestyle factors, with only a small number of cases due to underlying genetic disorders. Risk factors include diet, obesity, smoking, and lack of physical activity.
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