Activation and proliferation of cancer stem cells exert an important role in the invasion, metastasis, and recurrence of malignant tumors, including lung cancer. Therefore, exploring molecular targets related to self-renewal and mobility of lung cancer stem cells has important clinical significance. In our present study, we aimed to explore the effects of miR-138-5p on lung cancer stem-like cells and associated regulatory mechanism. In our present study, enhanced self-renewal capacity and elevated expression of cancer stem cells markers CD133, CD44, aldehyde dehydrogenase 1 of lung cancer stem-like cells derived from A549 cells were firstly verified. Then, obviously enhanced autophagy was found in lung cancer stem-like cells compared with parental cells A549. Besides, we found that enhanced autophagy induced by rapamycin promoted self-renewal and cell mobility of lung cancer stem-like cells and suppression of autophagy by 3-methyladenine exerted just opposite effects. In addition, miR-138-5p was found to be downregulated in lung cancer stem-like cells compared with that in parental cell A549. At the same time, overexpression of miR-138-5p by transfected with miR-138-5p mimic was found to effectively suppress self-renewal and invasion of lung cancer stem-like cells. Further study revealed that ATG7 was a target of miR-138-5p and overexpressed miR-138-5p suppressed ATG7-mediated autophagy. In addition, specific small interference RNA-ATG7 strengthened the inhibiting effect of miR-138-5p mimic on self-renewal and invasion of lung cancer stem-like cells. Taken together, we found that autophagy helped to maintain self-renewal and invasion ability of lung cancer stem-like cells and overexpressed miR-138-5p exerted anti-tumor effects by blocking the self-renewal and invasion of lung cancer stem-like cells through suppressing ATG7-mediated autophagy.
Background. Lymph node metastasis is an important route of lung cancer metastasis and can significantly affect the survival of lung cancer. Methods. All the analysis was conducted out in the R software. Expression profile and clinical information of lung adenocarcinoma (LUAD) patients were downloaded from The Cancer Genome Atlas database. Results. In our study, we firstly identified the characteristic genes of lymph node metastasis in LUAD through two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) logistic regression, and SVM-RFE algorithms. Ten characteristic genes were finally identified, including CRHR2, ITIH1, PRSS48, MAS1L, CYP4Z1, LMO1, TCP10L2, KRT78, IGFBP1, and PITX3. Next, we performed univariate Cox regression, LASSO regression, and multivariate Cox regression sequentially to construct a prognosis model based on MAS1L, TCP10L2, and CRHR2, which had a good prognosis prediction efficiency in both training and validation cohorts. Univariate and multivariate analysis indicated that our model is a risk factor independent of other clinical features. Pathway enrichment analysis showed that in the high-risk patients, the pathway of MYC target, unfolded protein response, interferon alpha response, DNA repair, reactive oxygen species pathway, and glycolysis were significantly enriched. Among three model genes, MAS1L aroused our interest and therefore was selected for further analysis. KM survival curves showed that the patients with higher MAS1L might have better disease-free survival and progression-free survival. Further, pathway enrichment, genomic instability, immune infiltration, and drug sensitivity analysis were performed to in-deep explore the role of MAS1L in LUAD. Conclusions. Results showed that the signature based on MAS1L, TCP10L2, and CRHR2 is a useful tool to predict prognosis and lung cancer lymph node metastasis.
Aim The aim of this study was to identify clinical endoscopic indicators related to peri-ulcerative mucosal inflammation and to analyze whether the degree of peri-ulcerative mucosal inflammation appearance is an independent risk factor for gastric ulcer rebleeding. Methods We conducted a retrospective study that included patients with gastric ulcer bleeding who were hospitalized at three medical centers in China from January 1, 2016 to December 31, 2019. Ulcer rebleeding that occurred within 30 days of successful initial hemostasis was analyzed to determine whether this event was related to the degree of peri-ulcerative mucosal inflammation appearance or other mucosal inflammation-related factors. Results We enrolled 1111 patients and determined that GBS-Rebleeding-ROC (P<0.001), age (P=0.01), use of NSAIDs (P=0.001), bile reflux (P<0.001), and Helicobacter pylori (P<0.001) are all risk factors for peri-ulcerative mucosal inflammation appearance. Through multivariate analysis, we determined that severe peri-ulcerative mucosal inflammation appearance (P=0.002) was an independent risk factor for ulcer rebleeding within 30 days. Finally, we developed a risk assessment model using factors associated with mucosal inflammation that may be useful for early prediction of rebleeding. Conclusion The risk factors for peri-ulcerative mucosal inflammation appearance were identified. Severe peri-ulcerative mucosal inflammation appearance is an independent risk factor for ulcer rebleeding.
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