Circular RNAs (circRNAs) have been implicated in cancer progression through largely unknown mechanisms. Herein, we identify an N6-methyladenosine (m6A) modified circRNA, circNSUN2, frequently upregulated in tumor tissues and serum samples from colorectal carcinoma (CRC) patients with liver metastasis (LM) and predicts poorer patient survival. The upregulated expression of circNSUN2 promotes LM in PDX metastasis models in vivo and accelerates cancer cells invasion in vitro. Importantly, N6-methyladenosine modification of circNSUN2 increases export to the cytoplasm. By forming a circNSUN2/IGF2BP2/HMGA2 RNA-protein ternary complex in the cytoplasm, circNSUN2 enhances the stability of HMGA2 mRNA to promote CRC metastasis progression. Clinically, the upregulated expressions of circNSUN2 and HMGA2 are more prevalent in LM tissues than in primary CRC tissues. These findings elucidate that N6-methyladenosine modification of circNSUN2 modulates cytoplasmic export and stabilizes HMGA2 to promote CRC LM, and suggest that circNSUN2 could represent a critical prognostic marker and/or therapeutic target for the disease.

ERF transcription factors play important roles in regulating gene expression under abiotic and biotic stresses. The first member of the ERF gene family in wheat (Triticum aestivum L.) was isolated by screening a drought-induced cDNA library and designated as T. aestivum ethylene-responsive factor 1 (TaERF1), which encoded a putative protein of 355 amino acids with a conserved DNA-binding domain and a conserved N-terminal motif (MCGGAIL). The TaERF1 gene was located on chromosome 7A. Protein interaction assays indicated that TaERF1, with a putative phosphorylation site (TPDITS) in the C-terminal region, was a potential phosphorylation substrate for TaMAPK1 protein kinase. Deletion of the N-terminal motif enhanced the interaction of TaERF1 with TaMAPK1. The predicted TaERF1 protein contained three putative nuclear localization signals (NLSs), and three NLSs modulated synergistically the activity of subcellular localization. As a trans-acting factor, TaERF1 was capable of binding to the GCC-box and CRT/DRE elements in vitro, and of trans-activating reporter gene expression in tobacco (Nicotiana tabacum L.) leaves. Transcription of the TaERF1 gene was induced not only by drought, salinity and low-temperature stresses and exogenous ABA, ethylene and salicylic acid, but also by infection with Blumeria graminis f. sp. tritici. Furthermore, overexpression of TaERF1 activated stress-related genes, including PR and COR/RD genes, under normal growth conditions, and improved pathogen and abiotic stress tolerance in transgenic plants. These results suggested that the TaERF1 gene encodes a GCC-box and CRT/DRE element binding factor that might be involved in multiple stress signal transduction pathways.

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The prognostic, especially predictive, values of inflammation indexes in advanced colorectal cancer were not established. Therefore, the both values of neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in patients with initially metastatic colorectal cancer (mCRC) were investigated and compared. Samples were collected from 243 patients who were initially diagnosed with mCRC between 2005 and 2010 in the Sun Yat-sen University Cancer Center. Elevated NLR (p < 0.001), PLR (p = 0.008), and CEA (p < 0.001) were identified as statistically significant poor prognostic factors for overall survival (OS), while only NLR (p = 0.029) and CEA (p < 0.001) were validated as independent predictors. Univariate analysis identified elevated NLR (p < 0.001), PLR (p = 0.023), and CEA (p < 0.001) as statistically significant poor predict factors for the progression-free survival (PFS) of first-line chemotherapy, while NLR (p = 0.013) and CEA (p = 0.001) were independent. In addition, we observed significantly different OS (p < 0.001) and PFS (p < 0.001) among patients who had elevations in both NLR and CEA levels and those having one elevation or neither elevation. NLR, PLR, and CEA were significant predictors of OS and PFS in mCRC. However, only NLR and CEA play as independent. When coupled with CEA, NLR may lead to improved prognostic predictors.

BackgroundPoor nutritional status is associated with progression and advanced disease in patients with cancer. The prognostic nutritional index (PNI) may represent a simple method of assessing host immunonutritional status. This study was designed to investigate the prognostic value of the PNI for distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC).MethodsA training cohort of 1,168 patients with non-metastatic NPC from two institutions was retrospectively analyzed. The optimal PNI cutoff value for DMFS was identified using the online tool “Cutoff Finder”. DMFS was analyzed using stratified and adjusted analysis. Propensity score-matched analysis was performed to balance baseline characteristics between the high and low PNI groups. Subsequently, the prognostic value of the PNI for DMFS was validated in an external validation cohort of 756 patients with NPC. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of different prognostic scores.ResultsThe optimal PNI cutoff value was determined to be 51. Low PNI was significantly associated with poorer DMFS than high PNI in univariate analysis (P<0.001) as well as multivariate analysis (P<0.001) before propensity score matching. In subgroup analyses, PNI could also stratify different risks of distant metastases. Propensity score-matched analyses confirmed the prognostic value of PNI, excluding other interpretations and selection bias. In the external validation cohort, patients with high PNI also had significantly lower risk of distant metastases than those with low PNI (Hazards Ratios, 0.487; P<0.001). The PNI consistently showed a higher AUC value at 1-year (0.780), 3-year (0.793) and 5-year (0.812) in comparison with other prognostic scores.ConclusionPNI, an inexpensive and easily assessable inflammatory index, could aid clinicians in developing individualized treatment and follow-up strategies for patients with non-metastatic NPC.