Lung cancer is one of the leading causes of cancer-related death in developed countries. Despite decades of intensive efforts to comate this malignant disease, the prognosis of lung cancer remains unfavorable and is especially poor in advanced non-small cell lung cancer (NSCLC). Accumulating evidence indicate that one of the main causes of the poor outcome in NSCLC treatment is the innate resistance of NSCLC patients to anticancer drugs. However, the mechanism underling NSCLC development and drug resistance is not fully understood. Here we show that the mitochondrial class III NAD(+)-dependent deacetylase SIRT5 is overexpressed in human NSCLC and high expression of SIRT5 predicts poor survival. SIRT5 knockdown represses lung cancer cell growth and transformation in vitro and in vivo. Furthermore, we find that SIRT5 knockdown makes lung cancer cells more sensitive to drug (cis-diamminedichloroplatinum [CDDP], 5-fluorouracil [5-FU] or bleomycin) treatment in vitro and in vivo. Mechanically, we identify Nrf2, which is a core transcription factor for lung cancer growth and drug resistance, as a target of SIRT5. SIRT5 mRNA level is positively correlated with the expression of Nrf2 in lung cancer tissues and SIRT5 knockdown reduces the expression of Nrf2 and its downstream drug-resistance genes. Taken together, our findings implicate that SIRT5 as a protein responsible for growth and drug resistance in human NSCLC, and SIRT5 may serve as a potential prognostic factor and drug target for intervention.

Carcinoma cells hijack the epithelial-mesenchymal transition (EMT) for tumor dissemination. Paired-related homeobox 1 (PRRX1) has been identified as a new EMT inducer. However, the function of PRRX1 in gastric cancer has not been elucidated. In this study, we observed that PRRX1 expression levels were upregulated and positively correlated with metastasis and EMT markers in human gastric cancer specimens. PRRX1 overexpression had distinct effects on the cell morphology, proliferation, migration and invasion of BGC823 and SGC7901 gastric cancer cells both in vitro and in xenografts. PRRX1 overexpression resulted in the regulation of the EMT molecular markers N-cadherin, E-cadherin and vimentin as well as the levels of intranuclear β-catenin and the Wnt/β-catenin target c-Myc. Furthermore, the inhibition of the Wnt/β-catenin pathway by XAV939 offset the effects of PRRX1 overexpression. These findings demonstrate that PRRX1 promotes EMT in gastric cancer cells through the activation of Wnt/β-catenin signaling and that PRRX1 upregulation is closely correlated with gastric cancer metastasis.

Peroxiredoxin 2 (Prdx2) is a member of the peroxiredoxin family, which is responsible for neutralizing reactive oxygen species. Prdx2 has been found to be elevated in several human cancer cells and tissues, including colorectal cancer (CRC), and it influences diverse cellular processes involving cells' survival, proliferation, and apoptosis, which suggests a possible role for Prdx2 in the maintenance of cancer cell. However, the mechanism by which Prdx2 modulates CRC cells' survival is unknown. The current study aimed to determine the effect of elevated Prdx2 on CRC cells and to further understand the underlying mechanisms. The results of this study showed that Prdx2 was upregulated in CRC tissues compared with the matched noncancer colorectal mucosa tissues and that Prdx2 expression was positively associated with tumor metastasis and the TNM stage. In the LoVo CRC cell line, Prdx2 was upregulated at both the RNA and protein levels compared with the normal FHC colorectal mucosa cell line. In addition, the LoVo CRC cell line was significantly more resistant to hydrogen peroxide (H₂O₂)-induced apoptosis because of a failure to activate pro-apoptotic pathways in contrast to Prdx2 knockdown cells. Suppression of Prdx2 using a lentiviral vector-mediated Prdx2-specific shRNA in the LoVo cell line restored H₂O₂ sensitivity. Our results suggested that Prdx2 has an essential role in regulating oxidation-induced apoptosis in CRC cells. Prdx2 may have potential as a therapeutic target in CRC.

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It has been reported that miR-19a was up-regulated in gastric cancer (GC), playing an oncogenic role. However, the underlying mechanism is still unknown. Therefore, in our present study, we investigated the role of miR-19a in gastric tissues as well as 2 GC cell lines. In vivo in clinical tissue level, we have detected basal expression level of miR-19a using real-time reversal transcriptional PCR (RT-PCR); in addition, the relevance between expression of miR-19a and clinic-pathological information was also analyzed. In vitro in cell line level, miR-19a was ectopically expressed using over expression and knock-down strategy. It was found that the overexpression of miR19a was significantly associated with metastasis of GC and inferior overall prognosis on clinical tissue level; that promotes the proliferation, migration and invasion; and that overexpression of miR-19a can promote the epithelialmesenchymal transition through activating PI3K/AKT pathway. Blocking the PI3K/AKT pathway could cancel the effect of miR-19a. All together, our results suggest that miR-19a could be used as a promising therapeutic target in the treatment of GC.