Oncogenic miR-744 promotes prostate cancer growth through direct targeting of LKB1.

Abstract

Prostate cancer (PCa) is one of the most common malignancies worldwide, and with a limited number of treatments for this type of cancer, its incidence is rapidly increasing. Patients presenting with PCa are likely to experience disease recurrence, which represents a considerable clinical challenge. MicroRNAs (miRNAs) have been widely characterized as a critical regulator in a number of types of cancer, including PCa. miRNA-744 (miR-744) has been reported to be involved in cancer regulation; however, its role in PCa remained poorly understood. In a recent study, it was demonstrated that miR-744 was overexpressed in prostate tissue from PCa patients when compared with the surrounding tissues, and knockdown of miR-744 resulted in reduced cell growth. In addition, an increased population of apoptotic cells was detected upon miR-744 knockdown, together with a decrease in cell proliferation. Cell cycle analysis demonstrated a higher number of cells in the G1 phase and lower numbers in the S phase following miR-744 silencing. The levels of key proteins involved in cell cycle progression (cyclin D1, cyclin-dependent kinase 4, and proliferating cell nuclear antigen) were increased, whereas those proteins responsible for cell cycle inhibition (cyclin-dependent kinase inhibitor p21) were decreased. The tumor suppressor liver kinase B1 (LKB1) was revealed to be a potential target of miR-744, suggesting its potential mechanism of action. LKB1 levels were negatively correlated with miR-744, and LKB1 was indicated to be a direct target of miR-744. Furthermore, it was revealed that by targeting LKB1, miR-744 may regulate adenosine monophosphate-activated protein kinase (AMPK); the AMPK signaling pathway was activated by miR-744 knockdown, with subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway. Taken together, these results demonstrated that miR-744 promoted cell growth through the AMPK signaling pathway, by targeting LKB1. The present study revealed a novel insight into the biological function of miR-744 in PCa, and that miR-744 may be a potential therapeutic target.

• Authors: Minglei Zhang, Hai Li, Yun Zhang, Hongyan Li
• Journal: Oncology letters (Oncol Lett) Vol. 17 Issue 2 Pg. 2257-2265 (Feb 2019) ISSN: 1792-1074 [Print] Greece
• PMID: 30675291 (Publication Type: Journal Article)