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Abstract
BackgroundPhosphatase and tensin homologue (PTEN), as a tumor suppressor, plays vital roles in tumorigenesis and progression of prostate cancer. However, the mechanisms of PTEN regulation still need further investigation. We here report that a combination of four microRNAs (miR-19b, miR-23b, miR-26a and miR-92a) promotes prostate cell proliferation by regulating PTEN and its downstream signals in vitro.Methodology/Principal FindingsWe found that the four microRNAs (miRNAs) could effectively suppress PTEN expression by directly interacting with its 3’ UTR in prostate epithelial and cancer cells. Under-expression of the four miRNAs by antisense neutralization up-regulates PTEN expression, while overexpression of the four miRNAs accelerates epithelial and prostate cancer cell proliferation. Furthermore, the expression of the four miRNAs could, singly or jointly, alter the expression of the key components in the phosphoinositide 3-kinase (PI3K)/Akt pathway, including PIK3CA, PIK3CD, PIK3R1 and Akt, along with their downstream signal, cyclin D1.ConclusionsThese results suggested that the four miRNAs could promote prostate cancer cell proliferation by co-regulating the expression of PTEN, PI3K/Akt pathway and cyclin D1 in vitro. These findings increase understanding of the molecular mechanisms of prostate carcinogenesis and progression, even provide valuable insights into the diagnosis, prognosis, and rational design of novel therapeutics for prostate cancer.
Highlights
Prostate cancer is one of the most common malignant tumors in men, with the morbidity and mortality significantly increasing in China in recent years, the incidence of prostate cancer remains much lower compared to western countries such as Europe and the United States [1,2,3]
We constructed a series of luciferase reporter vectors containing the artificial target sites for the four miRNAs, full-length Phosphatase and tensin homologue (PTEN) 3’ UTR (PU), its relevant truncated fragment (PUA, PUB, PUC or PUD), and the mutant counterpart, respectively (Figure 1B)
We found that neutralizing miR-23b, miR-26a or miR-92a with relevant anti-miR inhibitors significantly increased the relative luciferase activity to 1.31±0.04 ~ 1.72±0.09 fold or 1.19±0.08 ~ 1.56±0.1 fold
Summary
Prostate cancer is one of the most common malignant tumors in men, with the morbidity and mortality significantly increasing in China in recent years, the incidence of prostate cancer remains much lower compared to western countries such as Europe and the United States [1,2,3]. The causes of prostate cancer are complex, with multiple genes involved in its pathogenesis [4] One of these genes is the tumor-suppressor gene, phosphatase and tensin homologue (PTEN), which is commonly lost or down-regulated in prostate cancers. Conclusions: These results suggested that the four miRNAs could promote prostate cancer cell proliferation by coregulating the expression of PTEN, PI3K/Akt pathway and cyclin D1 in vitro. These findings increase understanding of the molecular mechanisms of prostate carcinogenesis and progression, even provide valuable insights into the diagnosis, prognosis, and rational design of novel therapeutics for prostate cancer
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