miR-526b-3p inhibits lung cancer cisplatin-resistance and metastasis by inhibiting STAT3-promoted PD-L1.

Chemotherapy remains the primary treatment of advanced solid cancer, including lung cancer. However, as first-line treatment, cisplatin-based therapy is restricted by the frequent development of drug resistance. Increasing data showed that the programmed cell death protein ligand 1 (PD-L1) plays a vital role in regulating cisplatin resistance. However, the underlying mechanisms are not fully understood. We found that miR-526b-3p expression declined while PD-L1 was elevated in cisplatin-resistant lung cancer compared to that in cisplatin-sensitive lung cancer by analyzing clinical samples. Significantly, miR-526b-3p was associated with response to cisplatin negatively. We further demonstrated that miR-526b-3p reversed cisplatin resistance, suppressed metastasis, and activated CD8+ T cells in a STAT3/PD-L1-dependent manner. Thus, our findings extended the knowledge of PD-L1-mediated cisplatin resistance of lung cancer. In addition, the introduction of miR-526b-3p provided a new clue to improve the anti-tumor effects of the combination of immunotherapy and chemotherapy.

Lung computed tomography image segmentation based on U-Net network fused with dilated convolution.

PURPOSE: In order to solve the problem of accurate and effective segmentation of the patient's lung computed tomography (CT) images, so as to improve the efficiency of treating lung cancer. METHOD: We propose a U-Net network (DC-U-Net) fused with dilated convolution, and compare the results of segmented lung CT with DC-U-Net, Otsu and region growth. We use Intersection over Union (IOU), Dice coefficient, Precision and Recall to evaluate the performance of the three algorithms. RESULTS: Compared with the common segmentation algorithm Otsu and region growing, the segmented image of DC-U-Net is closer to the Ground truth. The IOU of DC-U-Net is 0.9627, and the Dice coefficient is 0.9743, which is close to 1 and much higher than the other two algorithms. CONCLUSION: We propose that the model can directly segment the original image automatically, and the segmentation effect is good. This model speeds up the segmentation, simplifies the steps of medical image segmentation, and provides better segmentation for subsequent lung blood vessels, trachea and other tissues.

Esophageal cancer detection based on classification of gastrointestinal CT images using improved Faster RCNN.

PURPOSE: Esophageal cancer is a common malignant tumor in life, which seriously affects human health. In order to reduce the work intensity of doctors and improve detection accuracy, we proposed esophageal cancer detection using deep learning. The characteristics of deep learning: association and structure, activity and experience, essence and variation, migration and application, value and evaluation. METHOD: The improved Faster RCNN esophageal cancer detection in this paper introduces the online hard example mining (OHEM) mechanism into the system, and the experiment used 1520 gastrointestinal CT images from 421 patients. Then, we compare the overall performance of Inception-v2, Faster RCNN, and improved Faster RCNN through F-1 measure, mean average precision (mAP), and detection time. RESULTS: The experiment shows that the overall performance of the improved Faster RCNN is higher than the other two networks. The F-1 measure of our method reaches 95.71%, the mAP reaches 92.15%, and the detection time per CT is only 5.3s. CONCLUSION: Through comparative analysis on the esophageal cancer image data set, the experimental results show that the introduction of online hard example mining mechanism in the Faster RCNN algorithm can improve the detection accuracy to a certain extent.

The long noncoding RNA ANRIL acts as an oncogene and contributes to paclitaxel resistance of lung adenocarcinoma A549 cells.

Long non-coding RNAs (lncRNAs) are a family of non-protein-coding RNAs that might affect Lung adenocarcinoma (LAD) chemo-resistance and most of them could be used as biomarkers and therapy targets. However, the potential function of lncRNA ANRIL contributed paclitaxel chemo-resistance in LAD is still unknown. This study aimed to observe the expression of ANRIL in LAD, evaluate its biological role in the resistance of LAD cells to paclitaxel and explore the apoptosis role in the ANRIL associated mechanism. Our results showed that ANRIL functioning as a potential oncogene was up-regulated in LAD, and promoted the acquisition of chemo-resistance in paclitaxel partly through the mitochondrial pathway by modulating the expression of apoptosis-related protein cleaved-PARP and Bcl-2. These findings might improve LAD patients' paclitaxel treatment and made ANRIL to be a new target for paclitaxel-based chemotherapy in LAD.

RBX1 expression is an unfavorable prognostic factor in patients with non-small cell lung cancer.

The purpose of this study was to assess the prognostic value of RBX1 in patients with non-small cell lung cancer (NSCLC). Quantitative real-time (RT-PCR) and western blot were used to evaluate the mRNA and protein expression of RBX1 in NSCLC and corresponding non-cancerous tissues. Immunohistochemistry was performed to examine the expression of RBX1 in 192 NSCLC tissue samples. Overall survival was evaluated by the Kaplan-Meier method and analyzed by the log-rank test between different groups. The results showed that the RBX1 expression was significantly higher in NSCLC tissues than the corresponding non-cancerous lung tissues. High RBX1 expression was related to poor tumor differentiation, advanced TNM stage, and lymph node metastasis. Patients with high RBX1 expression had poor overall survival than those with high expression levels, which was consistent with the results of the subgroup analysis. Multivariate analysis showed that high RBX1 expression was an unfavorable prognostic factor for NSCLC patients. Our study indicated that RBX1 might play an important role in the observation of prognosis in NSCLC and could be a valuable marker for predicting the treatment outcome in patients with NSCLC.

Sestrin2 expression is a favorable prognostic factor in patients with non-small cell lung cancer.

The purpose of this study was to evaluate the prognostic value of Sestirn2 in patients with non-small cell lung cancer (NSCLC). Quantitative real-time ( RT-PCR) and western blot were performed to investigate the mRNA and protein expression of Sestirn2 in NSCLC and corresponding non-cancerous tissues. Immunohistochemistry was used to detect the expression of Sestirn2 in 210 NSCLC tissue samples. Overall survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test between different groups. The results indicated that the Sestirn2 expression was significantly lower in NSCLC tissues than the corresponding non-cancerous lung tissues. Low Sestirn2 expression was related to poor tumor differentiation, advanced TNM stage, and lymph node metastasis. Patients with high Sestirn2 expression had longer overall survival than those with low expression levels, which was consistent with the results of the subgroup analysis. Multivariate analysis showed that high Sestirn2 expression was a favorable prognostic factor for NSCLC patients. Our study indicated that Sestirn2 could play an important role in the observation of prognosis in NSCLC and might be a valuable marker for predicting the treatment outcome in patients with NSCLC.

Activation of M3 muscarinic receptor by acetylcholine promotes non-small cell lung cancer cell proliferation and invasion via EGFR/PI3K/AKT pathway.

Acetylcholine (ACh), which can be synthesized and secreted by cancer cells, has been reported to play an important role in tumor progression. ACh acts its role through activation of its receptors, muscarinic receptor (mAChR), and nicotinic receptor (nAChR). As a member of mAChR, M3 muscarinic receptor (M3R) is often highly expressed in many cancers. Activation of M3R by ACh participates in the proliferation, differentiation, transformation, and carcinogenesis of cancer. However, the effect of M3R activation on non-small cell lung cancer (NSCLC) remains unclear. Here, our study found that ACh dose-dependently promoted the proliferation, invasion, and migration of NSCLC cells. After silencing of M3R, the biological functions of ACh in NSCLC cells were greatly attenuated. Furthermore, ACh stimulation increased the production of IL-8 and time-dependently induced the activation of EGFR, PI3K, and AKT through M3R. In addition, ACh stimulated the activation of PI3K and AKT via EGFR activity, and blocking of PI3K/AKT pathway by special inhibitor LY294002 suppressed the ACh-mediated proliferation, invasion, and migration of NSCLC cells. Taken together, these findings indicate that activation of M3R by ACh enhances the proliferation, invasion, and migration of NSCLC cells. ACh-induced activation of EGFR/PI3K/AKT pathway and subsequent IL-8 upregulation may be one of the important mechanisms of M3R function. Thus, M3R could be a potential therapeutic target for the treatment of NSCLC.

Knockdown of response gene to complement 32 (RGC32) induces apoptosis and inhibits cell growth, migration, and invasion in human lung cancer cells.

Response gene to complement 32 (RGC32) is a novel protein originally identified as a cell cycle activator and has been demonstrated to be overexpressed in a variety of human malignancies, including lung cancer. However, the potential role of RGC32 in lung cancer initiation and progression remains to be elucidated. In the present study, RNA interference mediated by plasmid expressing RGC32 short-hairpin RNA (shRNA) was utilized to knockdown RGC32 expression in human lung cancer LTE cells. We found that the mRNA and protein expression levels of RGC32 were significantly decreased in RGC32-specific shRNA-transfected cells in comparison with the untransfected and control shRNA-transfected cells. Furthermore, knockdown of RGC32 dramatically reduced cell proliferation, colony formation, and invasion and migration capacities of LTE cells in vitro. Specific down-regulation of RGC32 caused G0/G1 cell cycle arrest and eventual apoptosis. Meanwhile, Western blot analysis indicated that cells with stably knockdown of RGC32 showed decreased expression levels of Cyclin D1, Cyclin E, Bcl-2, matrix metalloproteinase (MMP)-2, and MMP-9, but increased expression levels of activate caspase-3, Bax, and cleaved poly (ADP-ribose) polymerase (PARP) in comparison with control shRNA-transfected cells. Taken together, our data suggest that RGC32 is involved in tumorigenesis of human lung cancer and may serve as a promising therapeutic target for lung cancer.