LncRNA DANCR Promotes Lung Cancer by Sequestering miR-216a.

BACKGROUND: Long noncoding RNAs (lncRNAs) are a new class of cancer regulators. Here, we aimed to investigate the diagnostic and therapeutic values of an lncRNA, differentiation antagonizing noncoding RNA (DANCR), in lung cancer. METHODS: Real-time polymerase chain reaction was used to compare DANCR levels in normal and cancerous lung tissues as well as lung cancer cells. Lentiviral transduction was used to induce DANCR overexpression or silencing in vitro, followed by monitoring cell proliferation, colony formation, and changes in microRNA-216a (miR-216a) expression. DANCR-specific small hairpin RNA transduction was used to establish cells with stable DANCR knockdown, and silenced cells were used to initiate lung tumor xenografts, followed by monitoring tumor growth. RESULTS: DANCR upregulation was seen in lung cancer, particularly in high-grade lung cancer tissues and aggressive cancer cells. Ectopic DANCR expression induced lung cancer cell proliferation and colony formation, whereas DANCR silencing induced opposing effects. The miR-216a level in cancer cells was negatively correlated with DANCR expression. The DANCR knockdown reduced the growth of tumor xenografts in vivo. CONCLUSION: DANCR upregulation is a potential indicator of aggressive lung cancer. Silencing of DANCR has great potential as a potent therapeutic strategy in lung cancer.

LncRNA PCAT-1 promotes tumour growth and chemoresistance of oesophageal cancer to cisplatin.

Oesophageal cancer (OC) is one of the most fatal malignancies in the world, and chemoresistance restricts the therapeutic outcome of OC. Long noncoding RNA (lncRNA) was reported to play roles in multiple cancer types. Yet, the function of lncRNA in chemoresistance of OC has not been reported. A lncRNA gene, PCAT-1, showed higher expression in OC tissues, especially higher in secondary OC compared with normal mucosa tissues. Overexpression of PCAT-1 increased the proliferation rate and growth of OC cells. Inhibition of PCAT-1 decreased proliferation and growth of OC cells, and increased cisplatin chemosensitivity. In a mouse OC xenograft model, PCAT-1 inhibition repressed OC growth in vivo. Therefore, PCAT-1 may potentially serve as a therapeutic target for treating OC. PCAT-1 promotes development of OC and represses the chemoresistance of OC to cisplatin, and silencing of PCAT-1 may be a therapeutic strategy for treating OC.

Endothelial PAS domain-containing protein 1 confers TKI-resistance by mediating EGFR and MET pathways in non-small cell lung cancer cells.

Mutations in epidermal growth factor receptor (EGFR) rendering it constitutively active is one of the major causes for metastatic non-small-cell lung cancer (NSCLC), and EGFR-targeted therapies utilizing tyrosine kinase inhibitors (TKIs) are often used clinically as the first-line treatment. But approximately half of NSCLC patients develop resistance to these therapies, where the MET proto-oncogene is amplified by EGFR through the hypoxia-inducible factor (HIF)-1α. Here we report that endothelial PAS domain-containing protein 1 (EPAS1), with 48% sequence identity to HIF-1α, specifically binds to TKI-resistant T790M EGFR, but not to wild-type EGFR, in NSCLC cell lines. Expression of EPAS1 enhances amplification of MET when simultaneously expressed with T790M EGFR but not with wild-type EGFR, and this enhancement is independent of ligand binding domain of EGFR. MET amplification requires EPAS1, since EPAS1 knock-down reduced MET levels. When NSCLC cells expressing T790M EGFR were treated with TKIs, reduced EPAS1 levels significantly enhanced the drug effect, whereas over-expression of EPAS1 increased the drug resistant effect. This EPAS1-dependent TKI-resistance was abolished by knocking-down MET, suggesting that EPAS1 does not cause TKI-resistance itself but functions to bridge EGFR and MET interactions. Our findings suggest that EPAS1 is a key factor in the EGFR-MET crosstalk in conferring TKI-resistance in NSCLC cases, and could be used as a potential therapeutic target in TKI-resistant NSCLC patients.

[Restoration of pathological changes of emphysema by angiogenesis factors: experiment of rats].

OBJECTIVE: To investigate whether intratracheal administration of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) restore the pulmonary function and pathology in emphysema, and research the mechanism of they restored pulmonary emphysema, and the pathogenesis of pulmonary emphysema. METHODS: Twenty-four Wistar rats were randomized into the 4 equal groups: bFGF group [receiving a single intratracheal instillation of porcine pancreatic elastase (PPE) 250 U/kg, and 4 weeks later receiving intratracheal instillation of bFGF 400 U once a week for 3 weeks), VEGF group (receiving a single intratracheal instillation of PPE 250 U/kg, and 4 weeks later receiving intratracheal instillation of VEGF 2 microg once a week for 3 weeks), control group [receiving a single intratracheal instillation of PPE 250 U/kg, and 4 weeks later receiving intratracheal instillation of normal saline (NS) once a week for 3 weeks], and normal group (receiving intratracheal instillation of NS in above-mentioned pattern). Four weeks after treatment, arterial blood sample was collected from the abdominal aorta to undergo blood gas analysis for assessment pulmonary function, and then the rata were killed with their lungs taken out to undergo pathological examination. Immunohistochemistry was performed to detect the CD34, markers of pulmonary capillary endothelial cells. RESULTS: There were no significant differences in the artery blood gas analysis among the four groups (all P > 0.05). The levels of mean alveoli number (MAN) of the bFGF and VEGF groups were (43 +/- 8)/HP and (44 +/- 9)/HP] respectively, both significantly higher than that of the control group [(30 +/- 6)/HP, both P < 0.01]. The levels of mean linear intercept (MLI) of the bFGF and VEGF groups were (196 +/- 38) microm and (194 +/- 38) microm respectively, both significantly lower than that of the control group [(288 +/- 68) microm, both P < 0.01). the mean alveoli area (MAA) level of the bFGF and VEGF groups were (9856 +/- 1864) microm(2) and (9804 +/- 1929) microm(2) respectively, both significantly lower than that of the control group [(14,525 +/- 3408) microm(2), both P < 0.01]. The percentages of CD34(+) cells of the bFGF and VEGF groups were (3.7 +/- 1.3)% and (2.6 +/- 1.2)% respectively, both significantly higher than that of the control group [(0.8 +/- 0.7)%, both P < 0.05). CONCLUSION: bFGF and VEGF can restore the pathological changes of experimental emphysema. The damage of pulmonary capillary may play an important role in the pathogenesis of pulmonary emphysema.