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Tryptophan 2,3‑dioxygenase (TDO2) is a key rate‑limiting enzyme in the kynurenine pathway and promotes tumor growth and escape from immune surveillance in different types of cancer. The present study aimed to investigate whether TDO2 serves a role in the development of ovarian cancer. Reverse transcription‑quantitative PCR and western blotting were used to detect the expression of TDO2 in different cell lines. The effects of TDO2 overexpression, TDO2 knockdown and TDO2 inhibitor on ovarian cancer cell proliferation, migration and invasion were determined by MTS, colony formation and Transwell assays. The expression of TDO2 in ovarian cancer tissues, normal ovarian tissues and fallopian tube tissues were analyzed using the gene expression data from The Cancer Genome Atlas and Genotype‑Tissue Expression project. Immune cell infiltration in cancer tissues was evaluated using the single sample gene set enrichment analysis algorithm. The present study found that RasV12‑mediated oncogenic transformation was accompanied by the upregulation of TDO2. In addition, it was demonstrated that TDO2 was upregulated in ovarian cancer tissues compared with normal ovarian tissues. TDO2 overexpression promoted proliferation, migration and invasion of ovarian cancer cells, whereas TDO2 knockdown repressed these phenotypes. Treatment with LM10, a TDO2 inhibitor, also repressed the proliferation, migration and invasion of ovarian cancer cells. The present study indicated that TDO2 can be used as a new target for the treatment of ovarian cancer.

Background Human papillomavirus (HPV) infection and viral proteins expression cause a number of epigenetic alterations leading to cervical carcinogenesis. The recent discovery of a large amount of histone methylation modifiers reveals important roles of these enzymes in regulating tumor progression. Methods The changes in expression of 48 histone methylation modifiers were assessed following knockdown of HPV16 E7 in CaSki cells. Lysine-specific demethylase 2A (KDM2A)-regulated microRNAs (miRNAs) in cervical cancer pathogenesis were disclosed using quantitative real-time polymerase chain reaction. The function of KDM2A-miRNAs on cervical cancer was investigated in vitro and in vivo. Results Upregulation of KDM2A induced by HPV16 E7 promotes cervical cancer cell proliferation and invasion and is correlated with poor prognosis in patients with cervical cancer. KDM2A physically interacts with the promoter of miR-132 and suppresses its expression by removing the mono or dimethyl group from H3K36 at the miR-132 locus. Functionally, miR-132 represses cancer cell proliferation and invasion by inhibiting radixin (RDX). Upregulated KDM2A promotes cervical cancer progression by repressing miR-132, which results in a derepression of RDX. Therefore, KDM2A functions as a tumor activator in cervical cancer pathogenesis by binding miR-132 promoter and abrogating its tumor suppressive function. Conclusion Our results suggest a function for KDM2A in cervical cancer progression and suggest its candidacy as a new prognostic biomarker and target for clinical management of cervical cancer.

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.

Caloric restriction (CR) has been shown to promote longevity and ameliorate aging-associated diseases, including cancer. Extensive research over recent decades has revealed that CR reduces IGF-1/PI3K/AKT signaling and increases sirtuin signaling. We recently found that CR also enhances ALDOA/DNA-PK/p53 signaling. In the present review, we summarize the molecular mechanisms underlying the modulation of the IGF-1/PI3K/AKT pathway, sirtuin signaling, and the ALDOA/DNA-PK/p53 pathway by CR. We also summarize the evidence concerning the roles of these signaling pathways in carcinogenesis, and discuss how they are regulated by CR. Finally, we discuss the crosstalk between these signaling pathways.

Emerging evidence indicates that microRNAs play critical roles in carcinogenesis and cancer progression. In this study, miR-133a was found to be significantly downregulated in colon tumor tissues. We aimed to determine its biological function, molecular mechanisms, and direct target genes in colorectal cancer. From these results, we found that miR-133a was significantly downregulated in primary tumor tissues and colon cancer cell lines. Ectopic expression of miR-133a in colon cancer cell lines significantly suppressed cell growth, as evidenced by cell viability and colony formation assays, as well as reduced xenograft tumor growth in nude mice. However, the effect of miR-133a was abolished by the overexpression of eIF4A1. Moreover, miR-133a inhibited cellular migration and invasiveness. A luciferase activity assay revealed oncogene eukaryotic translation initiation factor 4A1 as a direct target gene of miR-133a, whose expression was inversely correlated with that of miR-133a. Our results demonstrate that miR-133a plays a pivotal role in colorectal cancer by inhibiting cell proliferation, invasion, and migration by targeting oncogenic eukaryotic translation initiation factor 4A1, which acts as a tumor suppressor and may provide a new potential therapeutic target in colorectal cancer.