Overexpression of miR-939-3p predicts poor prognosis and promotes progression in lung cancer.

BACKGROUND: Lung cancer is the main cancer-related deaths worldwide. In this study, we explored the clinical prognostic significance and functional role of miR-939-3p in lung cancer. METHODS: We analyzed the expression of miR-939-3p in lung cancer tissues and cells by qRT-PCR. The prognostic significance of miR-939-3p was investigated using the Kaplan-Meier survival and Cox regression analyses. The CCK-8 assay was used to determine the role of miR-939-3p in cell proliferation. Transwell assays were used to determine the effects of miR-939-3p on cell migration and invasion abilities. RESULTS: The expression of miR-939-3p was upregulated in cancer tissues and cell lines compared with adjacent normal tissues and normal cells, respectively. The upregulated miR-939-3p was significantly associated with lymph node metastasis, TNM stage and poor prognosis of lung cancer patients. After the transfection of miR-939 mimic, overexpression of miR-939-3p promoted lung cancer cell proliferation, migration, and invasion. CONCLUSION: These findings suggested that miR-939-3p acts as an oncogene and promotes cell proliferation, migration, and invasion in lung cancer. miR-939-3p may be a potential independent prognostic biomarker in lung cancer.

Effect of nutritional supplement on bone marrow-derived mesenchymal stem cells from aplastic anaemia.

Aplastic anaemia (AA) is characterised by pancytopenia resulting from a marked reduction in haemopoietic stem cells (HSC). The regulation of haemopoiesis depends on the interaction between HSC and various cells of the bone marrow (BM) microenvironment, including BM-derived mesenchymal stromal cells (BMSC). The purpose of this study was to analyse the biological effect of nutritional supplement (NS), a dietary supplement consisting of thirty-six compounds: amino acids, nucleotides, vitamins and micronutrients on the BMSC of AA rats. The AA rat model was established by irradiating X-ray (2·5 Gy) and intraperitoneal injections of cyclophosphamide (35 mg/kg; Sigma) and chloramphenicol (35 mg/kg; Sigma). Then AA rats were fed with NS in a dose-dependent manner (2266·95, 1511·3, 1057·91 mg/kg d) by intragastric administration. The effect of NS on the BMSC of AA rats was analysed. As compared with AA rats, NS treatment significantly improved these peripheral blood parameters and stimulated the proliferation of total femoral nucleated cells. NS treatment affected proliferative behaviour of BMSC and suppressed BMSC differentiation to adipocytes. Furthermore, NS treatment of AA rats accelerated osteogenic differentiation of BMSC and enhanced bone mineral density. Co-incubation of HSC with mesenchymal stromal cells and serum from AA rats subjected to high-dose NS markedly improved the yield of CD34+cells. Protein microarray analysis revealed that there were eleven differentially expressed proteins in the NS group compared with the AA rat group. The identified specific NS might be implicated in rehabilitation of BMSC in AA rats, suggesting their potential of nutritional support in AA treatment.

Downregulation of peroxiredoxin-1 by ß-elemene enhances the radiosensitivity of lung adenocarcinoma xenografts.

ß-elemene, the active component of elemene (1-methyl-1-vinyl-2,4-diisopropenyl-cyclohexane), is a naturally occurring compound isolated from the traditional Chinese medicinal herb Curcuma wenyujin. Studies have confirmed that ß-elemene enhances the radiosensitivity of lung cancer cell lines such as A549, by multiple pathways; however, their underlying mechanisms and pathways are yet to be elucidated. In the present study, two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry were used to profile the different proteins in A549 cell xenograft models of both treatment groups. The protein/mRNA expression was assessed by reverse transcription-polymerase chain reaction and western blotting techniques in tumor samples from all treatment groups. As a critical player in redox regulation of cancer cells, inhibition of peroxiredoxin-1 (Prx-1) may be an effective option for enhancing the tumor response to radiation. We further verified Prx-1 expression at the transcription and translation levels. ß-elemene at a dose of 45 mg/kg had little effect on the Prx-1 protein expression, which was correlated with a moderate antitumor effect. However, a 45 mg/kg dose of ß-elemene significantly inhibited the Prx-1 mRNA expression, thereby suggesting a possible influence on the transcriptional process, and radiation significantly increased the Prx-1 mRNA/protein expression compared to the control group (p<0.01). Notably, Prx-1 mRNA/protein expression was significantly lower in the ß-elemene/radiation co-treatment group compared to the baseline levels in the control group (p<0.01). These results suggest that radiation-induced Prx-1 expression is directly or indirectly suppressed by ß-elemene, thus suggesting a new pathway by which to reverse radioresistance.

Down-regulation of survivin and hypoxia-inducible factor-1 α by ß-elemene enhances the radiosensitivity of lung adenocarcinoma xenograft.

Elemene (1-methyl-1-vinyl-2,4-diisopropenyl-cyclohexane) is a naturally occurring compound that can be isolated from the traditional Chinese medicinal herb Curcuma wenyujin. ß-elemene, its active component, has recently been demonstrated to enhance the radiosensitivity of human cancer cell lines in vitro and of one animal tumor in vivo. The underlying mechanism, however, is still unclear. In this study, we demonstrated for the first time that ß-elemene significantly improves the radiosensitivity of A549 lung adenocarcinoma xenograft in vivo as measured by tumor regrowth delay experiments. Our results showed that ß-elemene, at 45 mg/kg, significantly inhibited radiation-induced expression of survivin and hypoxia-inducible factor (HIF)-1 α proteins. Because HIF-1 α is known to regulate survivin transcription and acts as upstream regulator of survivin, it is possible that ß-elemene regulates the transcription of survivin through HIF-1 α. Our study suggests that ß-elemene is a promising drug to enhance tumor radioresponse, and survivin and HIF-1 α are novel targets of ß-elemene.