Purpose: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. This study aimed to explore the prognostic value of lncRNAs in CRC. Material and methods: We performed gene expression profiling to identify differentially expressed lncRNAs between 51 normal and 646 tumor tissues from The Cancer Genome Atlas database. Cox regression and robust likelihood-based survival models were used to find prognosis-related lncRNAs. A lncRNA signature was developed to predict the overall survival of patients with CRC. In addition, a receiver operating characteristic curve analysis was performed to identify the optimal cutoff with the best Youden index to divide patients into different groups based on risk level. Results: Eighty survival-related lncRNAs were identified and a 15-lncRNA signature was developed on the basis of a risk score to comprehensively predict the overall survival of patients with CRC. The prognostic value of the 15-lncRNA risk score was validated using the internal testing set and total set. The risk indicator was shown to be an independent prognostic factor (hazard ratio =2.92; 95% CI: 1.73–4.94; P<0.001). Notably, all 15 lncRNAs (AC024581.1, FOXD3-AS1, AC012531.1, AC003101.2, LINC01219, AC083967.1, AL590483.1, AC105118.1, AC010789.1, AC067930.5, AC105219.2, LINC01354, LINC02474, LINC02257, and AC079612.1) were newly found to correlate with the prognosis of patients with CRC. Furthermore, the function of 15 lncRNAs was explored through the ceRNA network. These lncRNAs regulated coding genes that were involved in many key cancer pathways. Conclusion: A 15-lncRNA expression signature was discovered as a prognostic indicator for patients with CRC, which may act as competing endogenous RNA (ceRNAs) to play a crucial role in the modulation of cancer-related pathways. These findings may allow a better understanding of the prognostic value of lncRNAs.

Ferroptosis is a type of regulated cell death that displays a promising therapeutic pathway for drug‐resistant tumor cells. However, some pancreatic cancer (PC) cells are less sensitive to erastin‐induced ferroptosis, and normal pancreatic cells are susceptible to this newly discovered cell death. Therefore, there is an urgent need to find drugs to enhance the sensitivity of these PC cells to erastin while limiting side effects. Here, we found that the oxidized form of vitamin C‐dehydroascorbic acid (DHA) can be transported into PC cells expressing high levels of GLUT1, resulting in ferroptosis. Moreover, pharmacological vitamin C combined with erastin can synergistically induce ferroptosis of PC cells involving glutathione (GSH) reduction and ferrous iron accumulation while inhibiting the cytotoxicity of normal cells. Mechanistically, as a direct system Xc^- inhibitor, erastin can directly suppress the synthesis of GSH, and the recycling of vitamin C and DHA is performed through GSH consumption, which is denoted as the classical mode. Furthermore, oxidative stress induced by erastin and vitamin C could enhance the expression of HMOX1 via the AMP‐activated protein kinase (AMPK)/nuclear factor erythroid 2‐related factor 2 (NRF2) pathway to increase the labile iron level, which is named the nonclassical mode. In vivo experiments showed that erastin and vitamin C can significantly slow tumor growth in PC xenografts. In summary, the combination of erastin and vitamin C exerts a synergistic effect of classical and nonclassical modes to induce ferroptosis in PC cells, which may provide a promising therapeutic strategy for PC.

Backgrounds: A number of circular RNAs (circRNAs) have been identified in various cancer including F-box and WD repeat domain containing 7 (FBXW7) circular RNA (circ-FBXW7), which can suppress glioma cell growth. However, the role of circ-FBXW7 in colorectal cancer (CRC) remains unclear. We aimed to investigate the effect and mechanisms of circ-FBXW7 on CRC progression. Methods: The expression of circ-FBXW7 in CRC patients was detected by PCR. Stably knockdown of circ-FBXW7 (si circ-FBXW7) cell lines and overexpression of circ-FBXW7 (oe circ-FBXW7) cell lines were constructed by small interfering RNA method and plasmids transfection in CRC SW480 and SW620 cells. The functional experiments including cell proliferation, migration and invasion were carried out by cell counting kit-8 (CCK-8) assay, wound healing assay and trans well assay. The xenograft animal models were established to evaluate the effect and the underlying molecular mechanisms of circ-FBXW7 on CRC progression. Results: CRC samples had a significantly lower level of circ-FBXW7 compared to normal tissue. si circ-FBXW7 notably promoted the proliferation, colony formation, cell migration and invasion of CRC cell in vitro. On contrast, circ-FBXW7 overexpressed significantly suppressed CRC cell proliferation, migration and invasion. Similarly, si circ-FBXW7 stimulated the tumor growth and circ-FBXW7 overexpression repressed the tumor progression in SW480 and SW620 tumor models, which suggested that circ-FBXW7 could serve as a target biomarker of CRC. Further study found that si circ-FBXW7 up-regulated the mRNA and protein expressions of NEK2 and mTOR, and diminished the PTEN expression. Whereas, overexpressed circ-FBXW7 induced the tumor suppression via reversing the expressions of NEK2, mTOR, and PTEN. Conclusion: circ-FBXW7 plays a major role in controlling the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and may be a potential therapeutic target for CRC treatment. Graphical Circ-FBXW7 controls the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and its overexpression inhibits colorectal cancer cell migration and invasion, suggesting the potential therapeutic target for CRC treatment.

Objective: The study aimed to screen microRNAs (miRNAs) that can be used for the early detection of colorectal cancer (CRC) based on differential expression of miRNA in serum. Materials and methods: A three-stage study was designed with a total of 217 CRCs, 168 colorectal adenomas (CRAs), and 190 healthy controls (HCs). A quantitative reverse transcription polymerase chain reaction was performed in three stages. We screened 528 miRNA expression profiles in the sera of 40 patients (CRC n=20, CRA n=10, and HC n=10) for candidate miRNAs, then 210 serum samples (CRC n=90, CRA n=60, and HC n=60) were used for screening of candidate miRNAs. Three hundred and twenty-five independent individual samples (CRC n=107, CRA n=98, and HC n=120) were used to validate the most differentially-expressed miRNAs in the screening stage, and binary logistic regression was used in the validation stage. A receiver operating characteristic curve was drawn to evaluate the diagnostic accuracy. Results: A 5-serum miRNA panel (miRNA-1246, miRNA-202-3p, miRNA-21-3p, miRNA-1229-3p, and miRNA-532-3p) effectively distinguished CRCs from HCs with 91.6% sensitivity and 91.7% specificity. The area under the curve (AUC) was 0.960 (95% confidence interval [CI]: 0.937–0.983). In addition, the panel also accurately distinguished CRCs from CRAs with 94.4% sensitivity and 84.7% specificity. The AUC was 0.951 (95% CI: 0.922–0.980). Conclusion: Our 5-serum miRNA panel accurately distinguished CRCs from CRAs and HCs with high sensitivity and specificity. The 5-serum miRNA panel may be a promising prospect for application as a nonintrusive and inexpensive method for the early detection of CRC.

Background: Aberrant DNA methylation is a crucial epigenetic regulator that is closely related to the occurrence and development of various cancers, including breast cancer (BC). The present study aimed to identify a novel methylation-based prognosis biomarker panel by integrally analyzing gene expression and methylation patterns in BC patients. Methods: DNA methylation and gene expression data of breast cancer (BRCA) were downloaded from The Cancer Genome Atlas (TCGA). R packages, including ChAMP, SVA, and MethylMix, were applied to identify the unique methylation-driven genes. Subsequently, these genes were subjected to Metascape for GO analysis. Univariant Cox regression was used to identify survival-related genes among the methylation-driven genes. Robust likelihood-based survival modeling was applied to define the prognosis markers. An independent data set (GSE72308) was used for further validation of our risk score system. Results: A total of 879 DNA methylation-driven genes were identified from 765 BC patients. In the discovery cohort, we identified 50 survival-related methylation-driven genes. Finally, we built an eight-methylation-driven gene panel that serves as prognostic predictors. Conclusions: Our analysis of transcriptome and methylome variations associated with the survival status of BC patients provides a further understanding of basic biological processes and a basis for the genetic etiology in BC.

Gastric cancer is one of most common cancers worldwide. Studies have shown that small nucleolar RNAs (snoRNAs) play important roles in several cancers. In this study, we analyzed the snoRNAs that were differentially expressed between gastric tumors and normal tissues, identified survival-associated snoRNAs, and developed an eight-snoRNA signature to predict overall survival of patients with gastric cancer. Furthermore, we explored the clinical significance of the eight signature snoRNAs. The risk biomarker established by the eight snoRNA signature was an independent prognostic factor (hazard ratio = 3.43, 95% confidence interval: 1.93–6.09, P = 2.72e-05). Furthermore, we validated the expression pattern of those snoRNAs in different gastric cancer cell lines and 5 paired normal and tumor tissues by using real time quantification PCR. Knocking down U66, one of the eight snoRNAs, inhibited the cell proliferation. In conclusion, we identified an eight-snoRNA risk signature to predict overall survival of gastric cancer patients. Seven of these snoRNAs were associated with clinical features of the disease. Knocking down U66 inhibited cell proliferation. These findings provide new clues with prognostic and therapeutic implications in gastric cancer.