Background: NOP2/Sun domain 2 (NSUN2) is one of the important RNA methyltransferases catalyzing 5‐methylcytosine (m5C) formation and participates in many critical bioprocesses. However, the roles and underlying molecular mechanisms of NSUN2‐mediated m5C modification in colorectal cancer (CRC) remain unclear.Methods: To explore the NSUN2 expression in CRC, fresh tissue samples were collected and Nsun2 knockout mouse was constructed. In vitro and in vivo functional assays were conducted to assess the role of NSUN2. RNA array and bisulfite sequencing were used to investigate the potential targets. The mechanisms of NSUN2 function on SKIL were identified by m5C‐methylated‐RNA immunoprecipitation and RNA stability assays. Additionally, tissue microarray analysis was conducted and patient‐derived tumour xenograft mouse (PDX) models were used to define the potential therapeutic targets.Results: NSUN2 was highly expressed in CRC and correlated with poor CRC patient survival. Moreover, silencing NSUN2 suppressed CRC tumourigenesis and progression in Nsun2 knockout mouse models. In vitro and in vivo studies suggested that NSUN2 promoted colorectal cancer cell growth. Mechanistically, SKI‐like proto‐oncogene (SKIL) is positively regulated by NSUN2, and the NSUN2‐SKIL axis is clinically relevant to CRC. NSUN2 induced m5C modification of SKIL and stabilized its mRNA, which was mediated by Y‐box binding protein 1 (YBX1). Elevated SKIL levels increased transcriptional coactivator with PDZ‐binding motif (TAZ) activation.Conclusions: Our findings highlight the importance of NSUN2 in the initiation and progression of CRC via m5C‐YBX1‐dependent stabilization of the SKIL transcript, providing a promising targeted therapeutic strategy for CRC.

Pancreatic cancer is one of the deadliest tumours worldwide, and its poor prognosis is due to an inability to detect the disease at the early stages, thereby creating an urgent need to develop non-invasive biomarkers. P-element–induced wimpy testis (PIWI) proteins work together with piwi-interacting RNAs (piRNAs) to perform epigenetic regulation and as such hold great potential as biomarkers for pancreatic cancer. PIWIL2 and PIWIL4 are associated with better prognosis, while PIWIL1 and PIWIL3 involvement appears to be associated with carcinogenesis. We aimed to discover PIWIL3- and PIWIL4-modulated piRNAs and determine their potential mechanisms in pancreatic cancer and the clinical implications. PIWIL3 or PIWIL4 was downregulated in pancreatic cancer-derived cell lines or in a non-tumour cell line. Differentially expressed piRNAs were analysed by next generation sequencing of small RNA. Nine fresh-frozen samples from solid human pancreases (three healthy pancreases, three intraductal papillary mucinous neoplasms, and three early-stage pancreatic cancers) were included in the sequencing analysis. Two piRNAs associated with PIWIL3 (piR-168112 and piR-162725) were identified in the neoplastic cells; in untransformed samples, we identified one piRNA associated with PIWIL4 (pir-366845). After validation in pancreatic cancer-derived cell lines and one untransformed pancreatic cell line, these piRNAs were evaluated in plasma samples from healthy donors (n = 27) or patients with pancreatic cancer (n = 45). Interestingly, piR-162725 expression identified pancreatic cancer patients versus healthy donors in liquid biopsies. Moreover, the potential of the serum carbohydrate antigen 19-9 (CA19-9) biomarker to identify pancreatic cancer patients was greatly enhanced when combined with piR-162725 detection. The enhanced diagnostic potential for the early detection of pancreatic cancer in liquid biopsies of these new small non-coding RNAs will likely improve the prognosis and management of this deadly cancer.

A disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16) has been reported to be involved in the pathogenesis of solid cancers. However, its role in gastric cancer (GC) is unclear. In this study, the role of ADAMTS16 in gastric cancer was investigated. The effects of ADAMTS16 on cell migration, invasion, and proliferation were investigated by functional experiments in vivo and in vitro. Downstream signal pathways of ADAMTS16 were confirmed by using bioinformatics analysis, co-immunoprecipitation, and immunofluorescence. Meanwhile, bioinformatics analysis, qRT-PCR, western blot, and dual-luciferase reporter gene analysis assays were used to identify ADAMTS16 targets. The expression of ADAMTS16 in GC was analyzed in public datasets. The expression of ADAMTS16 and its correlations with the clinical characteristics of GC were investigated by immunohistochemistry. Ectopic ADAMTS16 expression significantly promoted tumor cell migration, invasion, and growth. Bioinformatics analysis and western blot showed that ADAMTS16 upregulated the IFI27 protein through the NF-κb pathway, which was confirmed by immunofluorescence and western blot. Dual-luciferase reporter gene analysis identified a binding site between P65 and IFI27 that may be directly involved in the transcriptional regulation of IFI27. IFI27 knockdown reversed the promoting effect of ADAMTS16 on cell invasion, migration, and proliferation indicating that ADAMTS16 acts on GC cells by targeting the NF-κb/IFI27 axis. ADAMTS16 was associated with poor prognosis in clinical characteristics. ADAMTS16 promotes cell migration, invasion, and proliferation by targeting IFI27 through the NF-κB pathway and is a potential progressive and survival biomarker of GC.

The senescence of mesenchymal stem cells (MSCs) is closely related to aging and degenerative diseases. Curcumin exhibits antioxidant and anti-inflammatory effects and has been extensively used in anti-cancer and anti-aging applications. Studies have shown that curcumin can promote osteogenic differentiation, autophagy and proliferation of MSCs. Liposome, as a nano-carrier, provides a feasible strategy for improving the bioavailability and controlled-release profile of curcumin.This study aimed to evaluate the effects of curcumin liposomes (Cur-Lip) on the senescence of rat bone marrow mesenchymal stem cells (rBMSCs). Based on network pharmacology, we predicted the targets and mechanisms of curcumin on senescence of MSC. 23 key targets of Cur were associated with MSC senescence were screened out and mitophagy signaling was significantly enriched. Cur-Lip treatment alleviated senescence of D-galactose (D-gal)-induced rBMSCs, protected mitochondrial function, and activated mitophagy, which may be related to mitochondrial fission. Inhibition of mitophagy attenuated the protective effects of Cur-lip on mitochondrial function and senescence of rBMSCs. Our findings suggested that Cur-Lip could alleviate senescence of rBMSC and improve mitochondrial function by activating mitophagy.

(1) Background: Drug-eluting bead transarterial chemoembolization (DEB-TACE) is increasingly used for unresectable colorectal liver metastases (CRLM), yet individualized prognostic tools are lacking. We developed and internally validated nomograms predicting overall survival (OS) and hepatic progression-free survival (hPFS). (2) Methods: In this single-center retrospective cohort, reported per the TRIPOD guideline, OS and hPFS were estimated by Kaplan–Meier methods, and independent predictors from multivariable Cox regression were assembled into nomograms. Internal validation combined 1000-sample bootstrap optimism-corrected concordance indices (C-index), a uniform shrinkage factor, a bootstrap calibration slope, and a LASSO–Cox sensitivity analysis. (3) Results: Among 63 patients (44 deaths; 42 intrahepatic-progression events), median OS was 10.9 months and median hPFS was 5.8 months. Independent OS predictors were baseline CEA, high liver tumor burden (≥10 lesions), CEA decline (protective), and second-line-or-beyond interventional therapy (corrected C-index: 0.796). Independent hPFS predictors were high liver tumor burden, CEA decline, and age (corrected C-index: 0.718). Nomogram-defined high-risk groups had markedly shorter OS (5.3 vs. 22.8 months) and hPFS (3.3 vs. 8.6 months; both p < 0.001). Grade ≥3 toxicity occurred in 6%. (4) Conclusions: In real-world DEB-TACE-treated CRLM, liver tumor burden and CEA dynamics dominated prognosis; the internally validated nomograms provide individualized estimates and risk stratification, pending external validation.

Background/Objectives: Indocyanine green fluorescence angiography (ICG-FA) images bowel perfusion during colorectal cancer resection. Randomised trials have not established a consistent reduction in anastomotic leak (AL), so attention has shifted to how the test should be deployed. We examined the determinants of ICG-driven intraoperative decision change. Methods: Retrospective analysis of 379 consecutive patients (273 colorectal cancer, 106 benign disease) undergoing elective colorectal resection with primary anastomosis and intraoperative ICG-FA at six Spanish centres. The outcome was an ICG-prompted change of the intended transection line. Associations were examined by logistic regression, with permutation testing and case-mix adjustment for between-centre comparisons. Results: ICG-FA changed the operative plan in 46 patients (12.1%), identically in cancer and benign disease (12.1% versus 12.3%). No patient-level preoperative characteristic was associated with decision change (all ten candidates p > 0.20); odds ratios for malignant diagnosis, rectal location and neoadjuvant therapy were within 0.03 of unity. Two factors did predict it: left-sided or rectal resection versus right hemicolectomy (15.0% versus 4.3%; OR 3.96, 95% CI 1.38-11.37) and treating centre (0-18.1%; p = 0.021), both persisting in a mutually adjusted model (adjusted OR 6.75, 2.21-20.60 and 5.25, 2.38-11.58). AL occurred in 25 patients (6.6%); neoadjuvant therapy (adjusted OR 3.73) and rectal location (2.64) were independent predictors, decision change was not (1.88, 0.65-5.41). The higher crude leak rate after revision (10.9% versus 6.0%) reflects confounding by indication and must not be read as harm. Conclusions: Whether ICG-FA changes a colorectal cancer operation is determined by anatomical segment and treating centre, not by the patient's preoperative risk profile. Patient-level selection is therefore not feasible whereas segment-based targeting is, and the between-centre variation indicates that the intervention as delivered is not uniform.