Nasopharyngeal carcinoma (NPC) is a rare malignancy, with the unique geographical and ethnically characteristics of distribution. Gene chip and bioinformatics have been employed to reveal regulatory mechanisms in current functional genomics. However, a practical solution addressing the unresolved aspects of microarray data processing and analysis have been long pursuit. This study developed a new method to improve the accuracy of identifying key biomarkers, namely Unit Gamma Measurement (UGM), accounting for multiple hypotheses test statistics distribution, which could reduce the dependency problem. Three mRNA expression profile of NPC were selected to feed UGM. Differentially expressed genes (DEGs) were identified with UGM and hub genes were derived from them to explore their association with NPC using functional enrichment and pathway analysis. 47 potential DEGs were identified by UGM from the 3 selected datasets, and affluent in cysteine-type endopeptidase inhibitor activity, cilium movement, extracellular exosome etc. also participate in ECM-receptor interaction, chemical carcinogenesis, TNF signaling pathway, small cell lung cancer and mismatch repair pathway. Down-regulation of CAPS and WFDC2 can prolongation of the overall survival periods in the patients. ARMC4, SERPINB3, MUC4 etc. have a close relationship with NPC. The UGM is a practical method to identify NPC-associated genes and biomarkers.

The emergence of cancer stem cells (CSCs) is the barrier to effective clinical outcomes for Colon adenocarcinoma (COAD) patients. Autophagy was found to play an important role on CSCs stemness regulation. However, the specific role of autophagy-related genes in COAD stemness remains unclear. In this study, by processing on two independent stemness indices, mRNAsi and mDNAsi, TP53INP2 among 29 differentially expressed autophagy-related genes(ARGs) in COAD was identified to be the hub ARGs in COAD stemness elimination. COAD patients with high stemness indices scores usually showed a down-regulated TP53INP2 expression which was correlated to a higher chemotherapy resistance and poorer RFS than the others. Two TFs, KLF9 and SETBP1 were involved in CSCs TP53INP2 expression promotion. Additionally, the decreased expression level of TP53INP2 was found to be significantly correlated to the COAD immune subtypes of C4 which contributed to the immunoresistance with low density infiltration of TH2, Treg cells, macrophages, monocyte and dendritic cells. In conclusion, TP53INP2 was found to be a valid indicator for poor prognosis of COAD patients with high stemness. All these results would provide a new strategy in seeking potential COAD therapeutic targets.

The loss of cardiomyocytes (CMs) after myocardial infarction (MI) is widely acknowledged to initiate the development of heart failure (HF). Herein, we found that circCDYL2 (583 nt) derived from chromodomain Y-like 2 (Cdyl2) is significantly upregulated in vitro (oxygen-glucose deprivation (OGD)-treated CMs) and in vivo (failing heart post-MI) and can be translated into a polypeptide termed Cdyl2-60aa (~7 kDa) in the presence of internal ribosomal entry sites (IRES). Downregulation of circCDYL2 significantly decreased the loss of OGD-treated CMs or the infarcted area of the heart post-MI. Additionally, elevated circCDYL2 significantly accelerated CM apoptosis via Cdyl2-60aa. We then discovered that Cdyl2-60aa could stabilize protein apoptotic protease activating factor-1 (APAF1) and promote CM apoptosis; heat shock protein 70 (HSP70) mediated APAF1 degradation in CMs by ubiquitinating APAF1, which Cdyl2-60aa could competitively block. In conclusion, our work substantiated the claim that circCDYL2 could promote CM apoptosis via Cdyl2-60aa, which enhanced APAF1 stability by blocking its ubiquitination by HSP70, suggesting that it is a therapeutic target for HF post-MI in rats.