Re-expression of microRNA-4319 inhibits growth of prostate cancer via Her-2 suppression
- 171 Downloads
Her-2 is an epidermal growth factor receptor expressed in some prostate cancers (PC) associated with outgrowth of the tumor. Dysregulation of some microRNAs is involved in the regulation of PC pathogenesis, whereas the role of miR-4319 in PC is unknown and addressed in the current study.
The levels of miR-4319 in PC tissues were determined by RT-qPCR and their association with patient survival was studied by Kaplan–Meier analysis. Targeted genes for miR-4319 were predicted by a bioinformatics algorithm and confirmed by a dual-luciferase reporter assay. Growth of cells of overexpression or inhibition of miR-4319 or Her-2 was analyzed by an MTT assay. Cell survival in response to a chemotherapeutic drug, estramustine (EM), was analyzed by CCK-8 assay. Cell apoptosis was evaluated by TUNEL assay and Western blotting for apoptosis-associated proteins.
MiR-4319 levels were decreased in PC specimens, compared to corresponding normal prostate tissue. Lower levels of miR-4319 were correlated with poorer overall patients’ survival. In vitro, the cell survival mediated with Her-2 against chemotherapy was inhibited by overexpression of miR-4319 and was enhanced by depletion of miR-4319. Depletion of miR-4319 in primary prostate epithelial cells increased Her-2-dependent cell growth, while re-expression of miR-4319 in PC cells inhibited Her-2-dependent cell growth and Her-2-dependent resistance to EM-induced apoptosis.
The growth and chemo-resistance of PC cells may be suppressed via re-expression of miR-4319 that inhibits Her-2 signaling.
KeywordsProstate cancer (PC) miR-4319 Growth Chemotherapy Her-2
Compliance with ethical standards
Conflict of interest
The authors have declared that no competing interests exist.
Research involving human participants
40 clinical samples and correspondingly normal tissues (NT) were resected postoperatively from PC patients (PC, stage III), during 2009 and 2011 from The Fourth Hospital of Harbin Medical University. All patients signed the written informed consent. All the patients were diagnosed with pathological and/or cytological examinations done by experienced pathologists based on the WHO classification criteria. Samples were collected before patients receiving chemotherapy or radiotherapy. All the samples were immediately saved at − 70 °C for further amplification. The follow-up lasted for 5 years for all the patients.
For the use of these clinical materials for research purposes, prior patient consents and approval from the Institutional Research Ethics Committee were obtained.
- 13.Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. eLife. 2015; 4. https://doi.org/10.7554/eLife.05005.
- 14.Koie T, Mitsuzuka K, Yoneyama T, Narita S, Kawamura S, Kaiho Y, et al. Neoadjuvant luteinizing-hormone-releasing hormone agonist plus low-dose estramustine phosphate improves prostate-specific antigen-free survival in high-risk prostate cancer patients: a propensity score-matched analysis. Int J Clin Oncol. 2015;20(5):1018–25.CrossRefGoogle Scholar
- 23.Qin J, Ke J, Xu J, Wang F, Zhou Y, Jiang Y, et al. Downregulation of microRNA-132 by DNA hypermethylation is associated with cell invasion in colorectal cancer. OncoTargets Ther. 2015;8:3639–48.Google Scholar