ROLE OF MICRORNAS IN STRESS RESPONSE OF PROSTATE CANCER CELLS TO ARSENIC EXPOSURE

picture of Kari Hernandez presenting his/her poster: ROLE OF MICRORNAS IN STRESS RESPONSE OF PROSTATE CANCER CELLS TO ARSENIC EXPOSURE

Kari Hernandez , Micah Price, Ronald L. Heimark

ROLE OF MICRORNAS IN STRESS RESPONSE OF PROSTATE CANCER CELLS TO ARSENIC EXPOSURE

Many places in Arizona, such as the Colorado Plateau and Verde Valley, have high levels of arsenic in geological formations that contribute to ground water arsenic levels that exceed the EPA guideline of 10 parts per billion. High levels of arsenic in drinking water have been linked to cardiovascular diseases and urologic cancers— including prostate.  Prostate cancer is a clinically and biologically heterogeneous disease which can be indolent and localized or it can occur as an aggressive invasive disease that is metastatic.  MicroRNAs are small single stranded non-coding RNA molecules that regulate mRNA and protein levels by binding to the 3’ UTR of mRNAs in response to cell stress. MicroRNAs can keep the mRNA from being translated or lead to a degradation of the mRNA. PTEN (phosphatase and tensin homolog) is a tumor suppressor gene that is commonly lost in cancer cells; it is present in 20-40% of localized cancer cells and 60% of metastasis. PTEN is an inhibitor of the PI3K-Akt pathway—a pathway that leads to differentiation of cancer cells and metastasis. PTEN gene dosage is critical to proper regulation of the cell cycle, and PTEN is regulated by nearly 30 microRNAs. We find that the PTEN mRNA and protein levels are decreased over time in prostate cancer cells cultured in chronic arsenite for 20 weeks (2μM and 5μM). We used Dicer siRNA to determine if knockdown of Dicer would restore the level of PTEN in the chronic arsenite treated cells. Dicer is an enzyme that makes mature microRNAs—thus without Dicer microRNAs would not be produced and the microRNA’s effect on translation regulation would not be observed. We used Dicer siRNA to knockdown Dicer levels and western blotting and RT/PCR to analyze protein and mRNA levels of Dicer and PTEN. Further analysis will evaluate both which microRNAs are involved and the cancer stem cell properties of prostate cancer cells chronically exposed to arsenic. 

This research was supported by the “Native American Cancer Prevention” U54 grant from the NIH.

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