Inhibitory effect of miR-377 on the proliferative and invasive behaviors of prostate cancer cells through the modulation of MYC mRNA via its interaction with BCL-2/Bax, PTEN, and CDK4
Yasamin Azimi1, Sara Hajibabaei1, Ghazal Azimi2, Fatemeh Rahimi-Jamnani3 and Masoumeh Azizi1
1 Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
2 Department of Nanotechnology, Tehran Medical Branch, Islamic Azad University, Tehran, Iran
3 Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
Correspondence to: Masoumeh Azizi, email: [email protected], https://orcid.org/0000-0003-4679-3248
Keywords: miR-377; prostate cancer; MYC; PTEN; CDK4
Received: December 16, 2023 Accepted: April 24, 2024 Published: May 16, 2024
Abstract
The MYC gene is a regulatory and proto-oncogenic gene that is overexpressed in the majority of prostate cancers (PCa). Numerous studies have indicated that aberrant expression of microRNAs is involved in the initiation and progression of prostate cancer.
In this investigation, we assessed the impact of miR-377 on MYC through luciferase assay. Real-time PCR was employed to determine whether miR-377 could reduce the levels of MYC mRNA in transfected PCa cell lines (PC-3 and DU145) and change in the mRNA levels of BCL-2/Bax, PTEN, and CDK4 as a consequence of MYC downregulation. Moreover, we analyzed the effects of miR-377 on apoptosis, proliferation, cell cycle, and wound healing. Our findings demonstrate that miR-377 effectively targets MYC mRNA, as confirmed by luciferase assay and Real-time PCR. We observed a significant reduction in BCL-2 and CDK4 expression, along with an increase in Bax and PTEN, in prostate cancer cell lines upon MYC suppression. Additionally, elevated levels of miR-377 in PCa cell lines induced apoptosis, inhibited proliferation and migration, and arrested the cell cycle.
Taken together, these results unveil the inhibitory role of miR-377 in MYC function within PCa, thereby suggesting its potential as a therapeutic target for the treatment of this malignancy.
