N6-methyladenosine facilitates mitochondrial fusion of colorectal cancer cells via induction of GSH synthesis and stabilization of OPA1 mRNA.

Mitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA m6A accelerated mitochondria fusion of colorectal cancer (CRC) cells. Metabolomics analysis and function studies indicated that m6A triggered the generation of glutathione (GSH) via the upregulation of RRM2B-a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential. This in turn resulted in the mitochondria fusion of CRC cells. Mechanistically, m6A methylation of A1240 at 3'UTR of RRM2B increased its mRNA stability via binding with IGF2BP2. Similarly, m6A methylation of A2212 at the coding sequence (CDS) of OPA1-an essential GTPase protein for mitochondrial inner membrane fusion-also increased mRNA stability and triggered mitochondria fusion. Targeting m6A through the methyltransferase inhibitor STM2457 or the dm6ACRISPR system significantly suppressed mitochondria fusion. In vivo and clinical data confirmed the positive roles of the m6A/mitochondrial dynamics in tumor growth and CRC progression. Collectively, m6A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression, which facilitated cancer cell growth and CRC development.

Multi-omics analysis reveals PUS1 triggered malignancy and correlated with immune infiltrates in NSCLC.

Non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer. In this study, multi-omics analysis revealed a significant increase of pseudouridine synthase 1 (PUS1) in NSCLC and the high expression of PUS1 was associated with shorter OS (Overall Survival), PFS (Progression Free Survival), and PPS (Post Progression Survival) of NSCLC patients. Clinical subgroup analysis showed that PUS1 may be involved in the occurrence and development of NSCLC. Besides, TIMER, ESTIMATE, and IPS analysis suggested that PUS1 expression was associated with immune cell infiltration, and the expression of PUS1 was significantly negatively correlated with DC cell infiltration. GESA analysis also indicated PUS1 may involve in DNA_REPAIR, E2F_TARGETS, MYC_TARGETS_V2, G2M_CHECKPOINT and MYC_TARGETS_V1 pathways and triggered NSCLC malignancy through MCM5 or XPO1. Furthermore, PUS1 may be a potential target for NSCLC therapy.

Higher expression of pseudouridine synthase 7 promotes non-small cell lung cancer progression and suggests a poor prognosis.

BACKGROUND: Lung cancer is currently the second most common cancer, and non-small cell lung cancer accounts for about 85% of cases. NSCLC has not been studied for pseudouridine synthase 7 (PUS), a member of the PUS family that is associated with cancer development. Here, we focused on the role and clinical significance of PUS7 in non-small cell lung cancer. AIM: To explore the role of PUS7 in NSCLC and its clinical significance. METHODS: We downloaded datasets from the TCGA database and CPTAC database. In normal bronchial epithelial cells as well as NSCLC cell lines, RT-PCR and Western blot were used to quantify PUS7 expression. The role of PUS7 in NSCLC has been investigated by CCK8, migration assay, migration assay, and flow cytometry. PUS7 expression in tumor tissues was detected by immunohistochemical staining, and we evaluated the influence of PUS7 expression on the prognosis of NSCLC patients after surgery using Cox regression analysis, both univariate and multivariate. RESULTS: NSCLC cell lines and tissues expressed high levels of PUS7, and PUS7 was found to influence the proliferation, migration, and invasion of cancer cells without affecting their apoptosis. There was a worse prognosis for NSCLC patients who have higher PUS7 expression, suggesting that PUS7 was an independent indicator of prognosis (P = .05).

Preoperative weight loss is associated with poorer prognosis in operable esophageal cancer patients: A single-center retrospective analysis of a large cohort of Chinese patients.

Background: Preoperative weight loss has been shown to be a prognostic factor for many cancers. However, whether preoperative weight loss has clinical significance in patients with esophageal cancer is still controversial. Methods: A total of 2,174 Chinese patients underwent radical resection of esophageal cancer from 2000 to 2008 were included in our study. Patients were divided into two group: no weight loss (-) and weight loss (+), according to whether they had weight loss compared with their usual weight at diagnosis. The influence of preoperative weight loss on disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazard models. Results: weight loss (+) was significantly associated with age (P=0.001), alcoholism (P<0.001), tumor location (P=0.003), pT category (P=0.003), pN category (P=0.001). Patients of group weight loss (+) had significantly poorer DFS (Mean: 63.3 months (m) vs 76.8 m, P<0.001) and OS (67.4 m vs 83.3 m, P<0.001) than the no weight loss (-) group. In the final multivariate survival analysis with adjustment for covariates, we found that the weight loss (+) group had a 19% higher risk of death (HR=1.19, 95%CI: 1.07-1.33, P=0.002) and had a 13% higher risk of disease progression (HR=1.13, 95%CI: 1.01-1.25, P=0.027), respectively, than the no weight loss (-) group. Subgroup analysis indicated that the association with preoperative weight loss and better DFS or OS was observed in patients with esophageal squamous cell carcinoma (ESCC) and early pathological stage (I-II). Conclusion: Preoperative weight loss is associated with shorter OS and DFS, which means poor postoperative prognosis in esophageal cancer patients.