Search

Dietary restriction (DR) delays the incidence and decreases the growth of various types of tumors; however, the mechanisms responsible for DR-mediated antitumor effects have not been unequivocally identified. Here, we report that DR suppresses xenograft tumor growth by upregulating a novel signaling pathway. DR led to upregulated aldolase A (ALDOA) expression in xenograft tumors. ALDOA physically interacted with the catalytic subunit of DNA-dependent protein kinase (DNA-PK) and promoted DNA-PK activation. Activated DNA-PK phosphorylated p53 and increased its activity. Although ALDOA can function as an oncogene in cultured cells, it can also activate the tumor suppressor p53. Thus, ALDOA overexpression in the presence of p53 suppressed xenograft tumor growth; however, when p53 was suppressed, ALDOA overexpression promoted xenograft tumor growth. Moreover, we demonstrated that p53 suppression inhibited the antitumor effects of DR. Our results indicate that upregulation of the ALDOA/DNA-PK/p53 pathway is a mechanism accounting for the antitumor effects of DR.

Background We are committed to investigate miR-218-5 effects on the progression of cervical cancer (CC) cell and find out the molecular mechanism. Methods GSE9750 was obtained from GEO database and R Limma package was applied to filter out dysregulated genes. The pathways were enriched by GSEA software, ClusterProfiler and enrichplot packages to predict the function of DEGs. The binding sites of LYN were detected by miRanda and TargetScan. The miR2Disease database was used to find miRNAs related with CC. The expression of miR-218-5p and LYN were quantified by qRT-PCR and that of LYN protein was measured by western blot. The targeted relationships between miR-218-5p and LYN were verified by dual-luciferase reporter assay. Colony formation assays, wound healing, transwell invasion assay and flow cytometer analysis were performed to investigate the roles that miR-218-5p and LYN played in migration, invasion and death of cervical carcinoma. Xenografts established in nude mice were used to assess tumor growth in vivo. Results The highly expressed mRNA LYN was selected by microarray analysis in GSE9750. NF-κB signaling pathway was enriched base on GSEA results. The expression of miR-218-5p was lower but LYN was higher in CC primary tumors compared with normal control. In addition, miR-218-5p could regulate the expression of LYN in HeLa cells negatively. Overexpression of LYN could promote cell migration and invasion, but inhibit cell death in vitro, and also promote tumor formation in vivo via activating NF-κB signaling pathway which could be reversed by miR-218-5p. Conclusions MiR-218-5p suppressed the progression of CC via LYN/NF-κB signaling pathway.

Cancer is still a clinical challenge, with many efforts invested in order to achieve timely detection. Unexplained elevated blood carcinoembryonic antigen levels are occasionally observed in an asymptomatic population and considered as a risk factor of cancers. The purpose of this study was to determine the validity of 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-18 FDG-PET/CT) for detecting cancer in an asymptomatic population with an unexplained elevation in blood carcinoembryonic antigen (CEA) levels.This retrospective study included a total of 1920 asymptomatic examinees conducted from August 2011 through September 2013. The participants underwent CEA assay and conventional medical imaging (CEA-conventional), or CEA assay and F-18 FDG-PET/CT (CEA-PET/CT). The validity of conventional medical imaging and CEA-PET/CT scanning for detecting cancer and early-stage cancer in an asymptomatic population with an unexplained elevation in blood CEA levels were evaluated.Sensitivity, specificity, cancer detection rate, missed cancer detection rate, early-stage cancer detection rate, and early-stage cancer ratio using the CEA-PET/CT scanning were 96.6 %, 100 %, 10.4 %, 0.4 %, 3.7 %, and 34.5 %, respectively. In contrast, the corresponding values obtained using the conventional medical imaging were 50.6 % (P 0.0001), 100 % (P 0.9999), 50.6 % (P 0.0001), 99.9 % (P = 0.055), 2.6 % (P 0.0001), 2.5 % (P = 0.04), 0.7 % (P = 0.0004), and 14.5 % (P = 0.002), respectively.The F-18 FDG-PET/CT scanning significantly improved the validity of the cancer detection program in the asymptomatic population with an unexplained elevation in CEA levels.

Cigarette smoking might lead to lung cancer. However, the related signaling pathways at molecular level remained unknown until now. In this study, we studied the signaling processes associated between tobacco exposure and lung cancer. First, we detected and validated pathway-specific gene expression at bronchial epithelium. These proteins reflected the activation of signaling pathways relevant to tobacco exposure, including ATM, BCL2, GPX1, K-Ras, IKBKB, and SIRT1. Tobacco smoking was simulated via reactive oxygen species (ROS) pathway. ROS not only arrested cell cycle at G1/S stage but also increased expressions of Sirt1 and p27. Further studies showed that the expression of p27 was dependent on ERK1/2 activation, and p27 itself could halt cell cycle by inhibiting the activation of CDKs. Moreover, activation of K-Ras, the key regulator of Ras/ERK pathway, was tightly regulated by enzyme activity of Sirt1. Deacetylation of K-Ras by Sirt1 increased the transformation of Ras-GTP to Ras-GDP, promoting the activation of downstream of ERK1/2. In reverse, Ras/ERK pathway could also regulate Sirt1 transcription. In conclusion, inhibition of Sirt1 may be an effective strategy for the prevention of tumor progression in high-risk patients or as a therapeutic strategy in established tumors.