Prostate cancer (PCa) disproportionally affects African American men (AA) who have 60 percent higher incidence rate and twice the death rate of Caucasian men (CA), and is the second leading cause of cancer- related deaths in AA men probably due to a more aggressive disease. While socioeconomic factors contribute to this health disparity, they do not fully explain the differences in prostate cancer incidence, aggressiveness, and mortality among different ethnic groups. Non-coding RNAs, especially, miRNAs have emerged for their important gene regulatory function and their roles in regulating multiple coding genes and thereby modulate several biological pathways including cell proliferation, differentiation, apoptosis, metastasis and angiogenesis. Recent studies have identified distinct miRNA expression in serum of cancer patients and have suggested their usefulness as molecular targets and as biomarkers to predict progression from preneoplasia to cancer and outcome/prognosis of cancer patients. Very little is known about racial differences in the expression of these miRNA in cancers like prostate cancer that disproportionally affect AA men. Based on our preliminary data, we hypothesize that miRNA dysregulation in serum might be associated with PCa progression and PCa health disparities with potential to be developed as molecular target(s) and minimally invasive biomarker(s).
The specific aims are: (1) Study the expression of miR-101, miR-25 and miR-628-5p in prostate cancer where we will compare the expression of these miRNAs in (a) serum from 50 AA and 50 CA and (b) tissues from 50 AA and 50 CA prostate cancer patients by Q-PCR. (2) Examine the effects of miR-101, miR-25 and miR-628-5p gain- and loss-of-function on the neoplastic phenotype of prostate cancer and their oncogenic activity in normal prostate cells. This proposal will (i) establish a basis to study the expression pattern of these miRNAs in diverse serum samples and (ii) generate preliminary data for continued mechanistic investigation of miRNA biology in prostate cancer health disparities. Our future studies will validate these miRNAs in a wider population and examine the involvement of these miRNAs in the tumor biology of AA prostate cancer.
This R21 exploratory grant will generate data to support future research projects including basic science research and case control studies elucidating the role of these miRNAs in prostate cancer risk, validating miRNA targets, their regulation and biological functions. In the long term, these studies could have significant public health consequences as involvement of these miRNAs in African American prostate cancer will support their development as molecular targets and biomarkers for early detection, prevention and treatment of prostate cancer.
|Ramalinga, Malathi; Roy, Arpita; Srivastava, Anvesha et al. (2015) MicroRNA-212 negatively regulates starvation induced autophagy in prostate cancer cells by inhibiting SIRT1 and is a modulator of angiogenesis and cellular senescence. Oncotarget 6:34446-57|
|Tran, Anh Thu; Ramalinga, Malathi; Kedir, Habib et al. (2015) Autophagy inhibitor 3-methyladenine potentiates apoptosis induced by dietary tocotrienols in breast cancer cells. Eur J Nutr 54:265-72|
|Srivastava, Anvesha; Goldberger, Helle; Dimtchev, Alexander et al. (2014) Circulatory miR-628-5p is downregulated in prostate cancer patients. Tumour Biol 35:4867-73|
|Benabentos, Rocio; Ray, Payal; Kumar, Deepak (2014) Addressing health disparities in the undergraduate curriculum: an approach to develop a knowledgeable biomedical workforce. CBE Life Sci Educ 13:636-40|
|Srivastava, Anvesha; Goldberger, Helle; Dimtchev, Alexander et al. (2013) MicroRNA profiling in prostate cancer--the diagnostic potential of urinary miR-205 and miR-214. PLoS One 8:e76994|
|Srivastava, Anvesha; Suy, Simeng; Collins, Sean P et al. (2011) Circulating MicroRNA as Biomarkers: An Update in Prostate Cancer. Mol Cell Pharmacol 3:115-124|