MiR-33a and statins collaboratively reduce the proliferative capacity of prostate cancer cells

Abstract

Objective: Prostate cancer (PCa) is one of the leading causes of cancer deaths among men in the developedcountries. Accumulating data suggests a high-cholesterol Western diet as an important risk factor for PCa.Besides,significant evidencesassociate increased serum cholesterol levels with PCa development andprogression.In this study, we aimed at investigating the collaborative roles of cholesterol analogs, cholesterolloweringdrugs, and miR-33a, which is an important microRNA involved in regulation of cholesterolmetabolism,on the cellular phenotypes associated with PCa progression.Methods:We evaluated the effects of low-density lipoprotein (LDL) cholesterol, 25-hydroxycholesterol (25-HC), mevastatin and simvastatin on their ownand together with miR-33a on the proliferation, invasion andanchorage independent growthcapacity of PCa cells using Cell Counting Kit-8, Matrigel invasion, and softagar assays, respectively.Results: We show that cholesterol analogs significantly promoted proliferative, invasive, and clonogenicpotential of PCa cells, while cholesterol loweringstatins demonstrated opposite effects. Moreover, LDL and25-HC reversed the tumor suppressive potential of miR-33a and statin treatment promoted the proliferationinhibitory effect of miR-33a on PCa cells.Conclusions:We demonstrated that statins inhibited the cellular phenotypes associated with PCa progressionand miR-33a treatment strengthens the impacts of statins on cellular proliferation. These findings suggest thatstatins alone and together with miR-33a might be a useful tool for effective and successful eradication of PCacells.