Drug resistance is the major factor contributing to the failure of chemotherapy in non-small cell lung cancer (NSCLC) patients. Emerging evidence suggests that autophagy plays a vital role in the chemoresistance of many types of tumors. However, the exact mechanism underlying the chemoresistance of NSCLC is still elusive, and it is unclear whether lncRNA-XIST is involved in autophagy and chemoresistance of NSCLC. In the present study, we demonstrated that lncRNA-XIST was overexpressed in NSCLC tumor samples, and knockdown of lncRNA-XIST significantly decreased autophagy by regulation of ATG7 as determined by qPCR and by western blotting. Furthermore, we found that miR-17 was upregulated following knockdown of lncRNA-XIST, and miR-17 mimics decreased the protein levels of ATG7 by directly targeting the 3-untranslated region of ATG7 mRNA as determined by RT-qPCR and by western blotting. Furthermore, we found that the expression level of lncRNA-XIST was markedly increased in cisplatin-resistant A549 cells as determined by q-PCR. Knockdown of lncRNA-XIST restored the chemosensitivity of cisplatin-resistant A549 cells to cisplatin, which was reversed by miR-17 inhibitor and overexpression of ATG7 as determined by CCK8 assays. This study provides evidence that lncRNA-XIST may be a potential marker of poor response to cisplatin chemotherapy in NSCLC patients and the pathway ‘lncRNA-XIST/miR-17/autophagy’ may be a promising target for patients with chemoresistant NSCLC.
Published literatures on the prognostic value of hypoxia-inducible factor-1α (HIF-1α) overexpression in esophageal squamous cell carcinoma (ESCC) are conflicting and heterogeneous. We performed a meta-analysis to more precisely evaluate the clinicopathological and prognostic value of HIF-1α in patients with ESCC. Searches were applied to MEDLINE, Pubmed, Embase, Cochrane Library, Web of Science, and Chinese BioMedical Literature Databases until September 10, 2013, without language restrictions. The pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were used to estimate the effects. Twelve studies with 942 ESCC patients were selected to evaluate the correlation between HIF-1α and overall survival (OS), disease-free survival (DFS), response to chemoradiation (RC), and clinicopathological features. HIF-1α overexpression was significantly associated with poor OS (HR 1.78, 95% CI 1.41-2.24), DFS (HR 1.91, 95% CI 1.15-3.18), and RC (HR 3.56, 95% CI 1.68-7.53). Besides, HIF-1α overexpression was significantly associated with stage (OR 2.90, 95% CI 1.97-4.27), lymph node metastasis (OR 1.86, 95% CI 1.39-2.49), depth of invasion (OR 2.45, 95% CI 1.24-4.86), lymphatic invasion (OR 2.28, 95% CI 1.46-3.56), distant metastasis (OR 2.04, 95% CI 1.19-3.50), and vascular endothelial growth factor (OR 3.67, 95% CI 1.81-7.46). Our results indicate that HIF-1α overexpression can potently predict the poor prognosis and chemoradiation resistance for ESCC. Large prospective studies with multivariable survival analyses are now needed to confirm the clinical utility of HIF-1α as an independent prognostic marker.
Lung cancer causes serious health problems. Clinical diagnosis of lung cancer relies on histopathological evalution of tissue specimen. However, extensive knowledge of the metabolic biochemistry of tumors can potentially provide important information for accurate diagnosis of lung cancer. High resolution magic-angle spinning NMR spectroscopy has emerged and be widely acknowledged as an excellent tool in investigating tissue metabolism. Moreover, the combination of high resolution magic-angle spinning NMR technique and multivariate data analysis has become an important metabonomics platform for studying the intact biological tissues. This study reported the metabonomic characteristics of 51 lung tissues from 17 patients with lung cancer using the high resolution magic-angle spinning 1H NMR spectroscopy and the multivariate data analysis methods including principal component analysis and orthogonal partial least squares-discriminant analysis. Clear differences among the metabonomic characteristics of lung cancer tissues at various sites were disclosed. Compared with the adjacent noninvolved tissues, the lung cancer tissues had significantly high levels of aspartate, phosphocholine, glycerophosphocholine and lactate but significantly low levels of glucose and valine. Furthermore, significantly positive (or negative) correlations were observed between the levels of some metabolites such as lactate, fatty acids, valine, phosphocholine, and glycerophosphocholine. Magn Reson Med 66:1531-1540,
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