Function Of Piwi-Interacting Rnas In Prostate Cancer

Shunjia Zhang

This thesis is restricted to Yale network users only. It will be made publicly available on 08/28/2021



Background: As the most common cancer in male, prostate cancer makes up 9.5% of new cancer cases and 4.8% of all cancer death in US in 2018. Though the 5-year survival of prostate cancer is high and multiple treatments are available, the death rate of prostate cancer was still more than 19.5 per 100,000 men per year. With more and more evidence suggested that piRNA may play a more important role in tumorigenesis, we want to find out if piRNAs can be a potential treatment for prostate cancer.

Method: Two Prostate cancer cell lines (PC3, LNCap) and a normal prostate cell line (WPMY-1) were either transfected with piR-021163 at treatment group or single-stranded random RNA sequence as negative control group. MTS, wound healing and colony formation assay were done after transfection to detect cancer cell proliferation, migration and anchorage-independent growth in vitro which are crucial for carcinogenesis. Total RNA from cells were also extracted for genome-wide expression profiling. The result of mRNA array was analyzed with IPA software to find gene expression level differences between piR-021163 treated group and random RNA treated negative control group.

Result: The result of in vitro test showed that ipR-021163 has different impact on different prostate cancer cell lines. In PC3 cells, it showed significant (p<0.001) decrease in cell proliferation (72h after transfection), migration (24h after transfection) and anchorage-independent growth (after 2 weeks of transfection) when transfected with piR-021163 protective allele comparing with negative control group. But no significant different was observed in the LNCap cell line. IPA analysis suggested that TNF might be a core functionally interrelated molecule in piR-021163 functional pathway. And transfection of piR-021163 may lead to the decrease of inflammation of body cavity.

Conclusion: The role of piR-021163 in prostate cancer development and progression may be cancer subtype-specific. The cancer suppression effect of piR-021163 should be mediate through the activation TNF and is related with the inhibition of inflammation.