Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration.

摘要: Inorganic arsenic, an environmental contaminant and a human carcinogen is associated with prostate cancer. Emerging evidence suggests that cancer stem cells (CSCs) are the driving force of carcinogenesis. Chronic arsenic exposure malignantly transforms normal stem/progenitor cell (SC) line, WPE-stem to arsenic-cancer SCs (As-CSCs), through unknown mechanisms. MicroRNAs (miRNAs) small, non-coding RNAs negatively regulate gene expression at posttranscriptional level. In prior work, miR-143 was markedly downregulated in As-CSCs, suggesting role arsenic-induced malignant transformation. present study, we investigated whether loss important transformation SCs. Restoration As-CSCs achieved by lentivirus-mediated overexpression. Cells were assessed bi-weekly for up 30weeks examine mitigation phenotype. Secreted matrix metalloproteinase (MMP) activity increased transformation, but restoration decreased secreted MMP-2 MMP-9 enzyme activities compared scramble controls. Increased proliferation apoptotic resistance, two hallmarks cancer, upon restoration. apoptosis BCL2 BCL-XL expression. dysregulated SC/CSC self-renewal genes including NOTCH-1, BMI-1, OCT4 ABCG2. The anticancer effects overexpression appeared be mediated targeting inhibiting LIMK1 protein, phosphorylation cofilin, substrate. These findings clearly show mitigated multiple characteristics potential Thus, biomarker therapeutic target