Influence of fibroblasts on the expression of messenger RNAs and microRNAs in prostatic tumor cells (LNCaP)

• Grant number: 17/16271-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2017
• Effective date (End): October 31, 2018
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Flávia Karina Delella
• Grantee: Mariana Medeiros
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The prostate is an attached gland of the male reproductive system found in all mammals, playing an important role in reproduction. In humans, prostatic lesions are more common in middle-aged individuals, and prostate cancer (PCa) is the most prevalent type of cancer, and the second in the world between men. The interactions between prostatic glandular cells and their microenvironment are fundamental for the maintenance of organ homeostasis, providing proliferative and migratory restrictions. During the onset of malignant neoplasms, these restrictions are lost while the stroma adapts to the tumor. One example is fibroblasts modified by factors secreted by tumor cells, which become cancer-associated fibroblasts (CAFs), aiding in tumor development. Recent researches shows that other changes occur in cancer as the differential expression of small non-coding RNAs called microRNAs, which can act as oncogenes or tumor suppressors. MicroRNAs expressed by the prostate gland are differentially expressed by the constituent cells of lesions, such as the cells that originate the PCa. It is known that many of these microRNAs can act on or be regulated by extracellular matrix elements. Considering the importance of maintaining intact epithelio-stroma interactions as a way to prevent tumor development and progression, studies encompassing the regulation of the pathways involved in PCa by miRNAs are therefore extremely promising for the medical-scientific society and can contribute for the development of new diagnostic techniques and therapeutic strategies for patients with PCa. Our study may contribute with important results to this theme, since it aims to analyze the expression of 3 miRNAs related to the evolution of PCa (miR-21, miR-29b and miR-34a) and target molecules of these miRNAs involved in cell death processes (BAK-1, BCL-2 and BAX) and invasion (MMP-2 and TIMP-2) into prostate tumor cells (LNCaP) co-cultured with human fibroblasts (HFF-1). (AU)