We aimed to study the role of METTL3 in renal cell carcinoma (RCC) carcinogenesis and development. Immunohistochemistry was performed in clinical tissue microarray. Expression level of METTL3 in RCC tissues and cell lines was evaluated by quantitative real-time PCR (qRT-PCR) and western blot. Then, the effects of METTL3 on proliferation, migration, invasion and cell cycle were studied in RCC cells. Additionally, in vivo study was carried out in nude mice. Negative METTL3 expression was associated with larger tumor size (P=0.010) and higher histological grade (P=0.021). Moreover, RCC patients with positive METTL3 expression had an obvious longer survival time (P=0.039). METTL3 mRNA and protein expression was lower in RCC samples compared with adjacent non-tumor samples, and lower in RCC cell lines (CAKI-1, CAKI-2 and ACHN) compared with HK-2. Afterwards, knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest. In contrast, up-regulation of METTL3 could inhibit such functions and reduce G0/G1 arrest. Additionally, up-regulation of METTL3 significantly suppressed tumor growth in vivo. Furthermore, significant changes in epithelial-to-mesenchymal transition (EMT) and PI3K-Akt-mTOR pathways were observed. Overall, our findings demonstrated that METTL3 might have a carcinostasis role in cell proliferation, migration, invasion function and cell cycle of RCC, indicating METTL3 may act as a novel marker for tumorigenesis, development and survival of RCC.

Our purpose was to explore whether 68 Ga-PSMA PET/CT alone (PET/CT) or in combination with multiparametric MRI (PET/MRI) can improve the detection of clinically significant prostate cancer (PCa). Methods: We retrospectively enrolled 54 patients who underwent both MRI and PET/CT before radical prostatectomy. Regions of interest on MR images, PET/CT images, and pathologic images were marked. A lesion was defined as a region of interest marked on images obtained with any of the 3 modalities. All lesions were characterized using the prostate imaging reporting and data system (PI-RADS), the molecular imaging PSMA expression score, and the pathologic results and analyzed. Diagnostic performance was analyzed by receiver-operating-characteristic analysis. Specific improvement for lesions with different PI-RADS scores was analyzed using the net reclassification index (NRI). Results: In total, 90 lesions from 54 patients were analyzed, among which 66 lesions represented clinically significant PCa. Receiver-operating-characteristic analysis showed PET/MRI to perform better than MRI in detecting clinically significant PCa (change in area under the curve, 0.06; 95% confidence interval, 0.01-0.12; P , 0.05). With the calculated cutoff, PET/MRI performed significantly better than MRI (NRI, 21.9%; P , 0.01), with an improvement in sensitivity (89% vs. 76%, P , 0.01) at no sacrifice of specificity (96% vs. 88%, P . 0.05). Improvement in diagnosing clinically significant PCa occurred for lesions classified as PI-RADS 3 (NRI, 66.7%; P , 0.01). Conclusion: PET/MRI improves the detection of clinically significant PCa for PI-RADS 3 lesions.

Recently, long non-coding RNAs (lncRNAs) have been recognized as playing key roles in regulating cellular processes, such as proliferation, invasion, and metastasis. These lncRNAs have been shown to be abnormally expressed in tumorigenic processes. However, the role and clinical relevance of LUCAT1 in non-small-cell lung cancer (NSCLC) remain unclear. In this study, we found that the expression of LUCAT1 was significantly up-regulated in NSCLC tissues compared to non-tumor tissues, and its expression was associated with tumor size, tumor–node–metastasis (TNM) stage and overall survival (OS). Further experiments showed that LUCAT1 knockdown inhibited cell proliferation both in vitro and in vivo. Mechanistic investigations showed that LUCAT1 plays a key role in G0/G1 arrest. We further demonstrated that LUCAT1 was associated with polycomb repressor complexes (PRC2) and that this association was required for epigenetically repression of p21 and p57, thus contributing to the regulation of NSCLC cell cycle and proliferation. In summary, our results show that LUCAT1 could regulate tumorigenesis of NSCLC and be biomarker for poor prognosis in NSCLC.