Long noncoding RNA MEG3 regulates cell proliferation and apoptosis by disrupting microRNA-9-5p-mediated inhibition of NDRG1 in prostate cancer.

BACKGROUND: Long noncoding RNA MEG3 has been described to be involved in the regulation of gene expression and cancer progression. However, the role of lncMEG3 in prostate cancer (PCa) remains largely uncharted. METHODS: Differential expression of lncMEG3 was identified in PCa tissues using RNA-sequencing analysis. qRT-PCR was performed to examine the level of lncMEG3. Additionally, cellular fractionation and fluorescent in situ hybridization techniques were employed to determine the localization. Subsequently, functional assays were conducted to evaluate the impact of lncMEG3 and miR-9-5p on PCa proliferation and apoptosis in vitro and in vivo. The interaction between lncMEG3 and miR-9-5p was confirmed using RNA immunoprecipitation. Moreover, luciferase reporter assays were also utilized to investigate the relationship between miR-9-5p and NDRG1. RESULTS: We observed downregulation of lncMEG3 in PCa cells and tissues. Patients with lower levels of lncMEG3 had a higher likelihood of experiencing biochemical recurrence. Overexpression of lncMEG3 resulted in the inhibition of PCa cell proliferation and the promotion of apoptosis. Moreover, lncMEG3 is competitively bound to miR-9-5p, preventing its inhibitory effect on the target gene NDRG1. This ultimately led to the inhibition of PCa cell proliferation and the promotion of apoptosis. Furthermore, increasing lncMEG3 levels also demonstrated inhibitory effects on PCa proliferation and promotion of apoptosis in vivo. CONCLUSIONS: Our findings uncover a crucial role for lncMEG3 in inhibiting PCa proliferation and promoting apoptosis through disruption of miR-9-5p-mediated inhibition of NDRG1.

Preliminary clinical practice of radical prostatectomy without preoperative biopsy.

BACKGROUND: At present, biopsy is essential for the diagnosis of prostate cancer (PCa) before radical prostatectomy (RP). However, with the development of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and multiparametric magnetic resonance imaging (mpMRI), it might be feasible to avoid biopsy before RP. Herein, we aimed to explore the feasibility of avoiding biopsy before RP in patients highly suspected of having PCa after assessment of PSMA PET/CT and mpMRI. METHODS: Between December 2017 and April 2022, 56 patients with maximum standardized uptake value (SUVmax) of ≥4 and Prostate Imaging Reporting and Data System (PI-RADS) ≥4 lesions who received RP without preoperative biopsy were enrolled from two tertiary hospitals. The consistency between clinical and pathological diagnoses was evaluated. Preoperative characteristics were compared among patients with different pathological types, T stages, International Society of Urological Pathology (ISUP) grades, and European Association of Urology (EAU) risk groups. RESULTS: Fifty-five (98%) patients were confirmed with PCa by pathology, including 49 (89%) with clinically significant prostate cancer (csPCa, defined as ISUP grade ≥2 malignancy). One patient was diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN). CsPCa patients, compared with clinically insignificant prostate cancer (cisPCa) and HGPIN patients, were associated with a higher level of prostate-specific antigen (22.9 ng/mL vs. 10.0 ng/mL, P = 0.032), a lower median prostate volume (32.2 mL vs. 65.0 mL, P = 0.001), and a higher median SUVmax (13.3 vs. 5.6, P <0.001). CONCLUSIONS: It might be feasible to avoid biopsy before RP for patients with a high probability of PCa based on PSMA PET/CT and mpMRI. However, the diagnostic efficacy of csPCa with PI-RADS ≥4 and SUVmax of ≥4 is inadequate for performing a procedure such as RP. Further prospective multicenter studies with larger sample sizes are necessary to confirm our perspectives and establish predictive models with PSMA PET/CT and mpMRI.