Mechanism and clinical application of thymosin in the treatment of lung cancer.

Cancer is one of the leading causes of death worldwide. The burden of cancer on public health is becoming more widely acknowledged. Lung cancer has one of the highest incidence and mortality rates of all cancers. The prevalence of early screening, the emergence of targeted therapy, and the development of immunotherapy have all significantly improved the overall prognosis of lung cancer patients. The current state of affairs, however, is not encouraging, and there are issues like poor treatment outcomes for some patients and extremely poor prognoses for those with advanced lung cancer. Because of their potent immunomodulatory capabilities, thymosin drugs are frequently used in the treatment of tumors. The effectiveness of thymosin drugs in the treatment of lung cancer has been demonstrated in numerous studies, which amply demonstrates the potential and future of thymosin drugs for the treatment of lung cancer. The clinical research on thymosin peptide drugs in lung cancer and the basic research on the mechanism of thymosin drugs in anti-lung cancer are both systematically summarized and analyzed in this paper, along with future research directions.

A bibliometric analysis of Mediterranean diet on cancer from 2012 to 2021.

Background: Numerous studies have demonstrated the value of the Mediterranean diet (MD) as a nutritious eating regimen for lowering the risk of cancer. This study aims to discuss the research patterns, existing state, and possible hotspots in implementing the MD for the prevention and treatment of cancer using bibliometrics. Methods: The Web of Science Core Collection (WoSCC) was searched for articles on cancer that were related to the MD. CiteSpace, VOSviewer, Microsoft Excel 2019, and R software were utilized for bibliometric analysis and data visualization. Results: There were 1,415 articles and reviews published from 2012 to 2021. Annual publication volume showed a continuous upward trend. Italy and Harvard University were the country and institution, respectively, with the highest number of publications on this topic. Nutrients ranked first in the number of documents, number of citations, and the H-index. James R. Hebert was the most productive writer, and Antonia Trichopoulou was the most co-cited author. "Alcohol consumption," "oleic acid," and "low density lipoprotein" were keywords used in earlier publications, while more recent hotspots focused on "gut microbiota," "older adult," and "polyphenol." Conclusion: Over the past decade, research on the MD in the field of cancer has received increasing attention. To improve the level of evidence for the beneficial effects of the MD on a range of cancers, more research on molecular mechanisms and better clinical studies are required.

Relationship between Patients' Baseline Characteristics and Survival Benefits in Immunotherapy-Treated Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Background: The difference of patients' baseline characteristics such as sex, age, Eastern Cooperative Oncology Group performance status (ECOG PS), and smoking status may influence the immune response. However, little is known about whether these factors affect the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small-cell lung cancer (NSCLC). Therefore, we performed this systematic review and meta-analysis to investigate the relationship between patients' baseline characteristics and survival benefits in immunotherapy-treated NSCLC. Materials and Methods: We performed a systematic search of PubMed, the Cochrane Library, and Embase for randomized controlled trials (RCTs) of NSCLC immunotherapy. We also searched abstracts and presentations from the proceedings of the American Society of Clinical Oncology and the European Society of Medical Oncology to identify unpublished studies. These studies have available data based on patients' baseline characteristics (such as sex, age, ECOG PS, and smoking status). We take the hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS) as the effect index and use the random effect model to pool the results. Results: We included 18 phase II/III RCTs with a total of 14,189 participants. The benefits of ICIs were found for both male (pooled OS-HR 0.77, 95% CI 0.72-0.82, P < 0.05) and female patients (pooled OS-HR 0.77, 95% CI 0.67-0.87, P < 0.05); for both younger (<65 y: pooled OS-HR 0.74, 95% CI 0.68-0.81, P < 0.05) and older patients (≥65 y: pooled OS-HR 0.80, 95% CI 0.75-0.86, P < 0.05); and for both patients with ECOG PS = 0 (pooled OS-HR 0.77, 95% CI 0.71-0.84, P < 0.05) and ECOG PS ≥ 1 (pooled OS-HR 0.76, 95% CI 0.70-0.82, P < 0.05). Moreover, there was no significant difference in the efficacy of ICIs among different sex (P value for interaction = 0.955), age (P value for interaction = 0.17), or ECOG PS (P value for interaction = 0.765). However, in patients with different smoking status, the application of ICIs significantly prolonged the OS of smokers (pooled OS-HR 0.77, 95% CI 0.71-0.83, P < 0.05) but could not significantly improve the OS of never smokers (pooled OS-HR 0.85, 95% CI 0.70-1.03, P > 0.05). Conclusions: ICIs could significantly improve prognosis in patients with advanced NSCLC, regardless of sex, age, or ECOG PS. But among patients with different smoking status, the survival benefits of never smokers treated with ICIs were no better than that of controls. The impact of these factors on immunotherapy should be considered in the future clinical practice and guidelines.

Circular RNA circ-PTEN elevates PTEN inhibiting the proliferation of non-small cell lung cancer cells.

Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor in various cancer types, including non-small cell lung cancer (NSCLC). Circular RNA (circRNA) has recently been proven to be strongly linked with cancer progression. Here, we aimed to investigate the biological relevance and clinical significance of circRNA derived from PTEN in NSCLC. We found that circ-PTEN (hsa_circ_0094342) was significantly decreased in NSCLC tissues and serum, which was attributed to the upregulation of RNA-binding protein DHX9. Low circ-PTEN was linked with malignant clinical features and poor outcome. Exogenous expression of circ-PTEN markedly inhibited NSCLC cell proliferation in vitro as well as retarded tumor growth in vivo. Circ-PTEN increased the expression of its host gene PTEN via acting as a sponge for miR-155 and miR-330-3p, leading to the inactivation of the carcinogenic PI3K/AKT signaling pathway. The xenograft tumor model also indicated the existence of circ-PTEN/miR-155/miR-330-3p/PTEN regulatory axis in vivo. Our data for the first time demonstrate that circ-PTEN functions as a tumor-inhibiting circRNA in NSCLC through post-transcriptionally regulating PTEN, hinting a promising diagnostic/prognostic biomarker as well as therapeutic target for NSCLC patients.

Circular RNA circ-SLC7A6 acts as a tumor suppressor in non-small cell lung cancer through abundantly sponging miR-21.

Circular RNA (circRNA) is currently considered to be a key regulatory molecule in cancer biology. In the present study, we aimed to explore the functional and clinical roles of circ-SLC7A6 (a circRNA derived from SLC7A6 gene) in non-small cell lung cancer (NSCLC). Circ-SLC7A6 was significantly downregulated in NSCLC tissues in comparison to para-carcinoma tissues. Low circ-SLC7A6 was closely associated with larger tumor size, lymph node metastasis, advanced clinical stage and adverse outcome. Exogenous expression of circ-SLC7A6 evidently inhibited the proliferation and invasion of NSCLC cells. Further investigations revealed that miR-21 was the direct functional target of circ-SLC7A6, in which circ-SLC7A6 abundantly sponged miR-21 and elevated a cohort of tumor suppressors, thus inhibiting NSCLC progression. Interestingly, QKI, elevated by circ-SLC7A6, could directly bind to the introns flanking circ-SLC7A6 to facilitate circ-SLC7A6 production. Importantly, in vivo xenograft tumor experiments showed that reintroduction of circ-SLC7A6 retarded tumor growth as well as decreased lung metastatic nodules. Overall, our study demonstrates that circ-SLC7A6 is a novel tumor suppressor in NSCLC, targeting circ-SLC7A6/miR-21 axis may be a promising treatment for NSCLC patients.

Cathepsin A knockdown decreases the proliferation and invasion of A549 lung adenocarcinoma cells.

Cathepsin A (CTSA) is a lysosomal protease that is abnormally expressed in various types of cancer; however, the function of CTSA in lung adenocarcinoma (LUAD) is unknown. The aim of the present study was to investigate the role of CTSA during LUAD development in vitro. The Cancer Genome Atlas (TCGA) database was used to analyze the expression of CTSA mRNA in LUAD tissues. CTSA was significantly upregulated in LUAD tissues compared with normal lung tissues. To explore the effect of CTSA on LUAD in vitro, LUAD A549 cells were transfected with CTSA small interfering RNA and the hallmarks of tumorigenesis were investigated using cell proliferation, cell cycle, wound healing, invasion and western blot assays. Following CTSA knockdown, proliferation of LUAD cells was decreased and an increased proportion of LUAD cells were arrested at the G0/G1 phase, with altered expression of critical cell cycle and proliferative marker proteins, including p53, p21 and proliferating cell nuclear antigen. Moreover, CTSA knockdown decreased the migration and invasion of A549 cells, as determined by wound healing, invasion, and western blotting assays. The expression levels of key proteins involved in epithelial­mesenchymal transition were analyzed by western blotting. CTSA knockdown enhanced the expression of E­cadherin, but decreased the expression of N­cadherin and ß­catenin in A549 cells. To the best of our knowledge, the present study suggested for the first time it has been identified that CTSA may serve as a tumor promoter in LUAD, enhancing the malignant progression of LUAD cells by promoting cell proliferation, migration and invasion. The results suggested that CTSA may serve as a novel therapeutic target for LUAD.

MiR-338 regulates NFATc1 expression and inhibits the proliferation and epithelial-mesenchymal transition of human non-small-cell lung cancer cells.

BACKGROUND: It is well known that nuclear factor of activated T cells c1 (NFATc1) expression is closely associated with progression of many cancers. And we found that miR-338 could directly target the NFATc1. However, the precise mechanisms of miR-338 in non-small-cell lung cancer (NSCLC) have not been well clarified. Our study aimed to explore the interaction between NFATc1 and miR-338 in NSCLC. METHODS: Quantitative RT-PCR was utilized to determine the expressions of NFATc1 and miR-338 in NSCLC tissues and cell lines. And the cell proliferation and epithelial-mesenchymal transition (EMT) were assessed to determine the functional roles of miR-338 and NFATc1 in NSCLC cells. NFATc1 expression was detected using quantitative RT-PCR and western blotting, respectively. Luciferase reporter assays were performed to validate NFATc1 as a target of miR-338 in NSCLC cells. RESULTS: In this study, our results showed that NFATc1 expression was significantly up-regulated in NSCLC tissues and cell lines, and the miR-338 level was dramatically down-regulated. Moreover high NFATc1 expression was closely associated with low miR-338 level in NSCLC tissues. Moreover introduction of miR-338 significantly inhibited proliferation and EMT of NSCLC cells. Bioinformatics analysis predicted that the NFATc1 was a potential target gene of miR-338. We demonstrated that miR-338 could directly target NFATc1 by using luciferase reporter assay. Besides, knockdown of NFATc1 had the similar effects with miR-338 overexpression on NSCLC cells. Up-regulation of NFATc1 in NSCLC cells partially abolished the inhibitory effects of miR-338 mimic. CONCLUSIONS: Overexpression of miR-338 inhibited cell proliferation and EMT of NSCLC cells by directly down-regulating NFATc1 expression.

MicroRNA-652 inhibits the biological characteristics of esophageal squamous cell carcinoma by directly targeting fibroblast growth factor receptor 1.

Numerous studies have demonstrated that microRNAs (miRNAs) are dysregulated in esophageal squamous cell carcinoma (ESCC). Changes in miRNA expression may be associated with ESCC formation and progression. Therefore, the identification of ESCC-associated miRNAs may facilitate the development of effective therapeutic approaches for patients with ESCC. Recently, miRNA-652 (miR-652) was recognized as a cancer-associated miRNA in a number of different types of cancer. However, the expression status and roles of miR-652 in ESCC as well as the molecular mechanisms modulated or altered by it remain largely unknown. In the present study, it was demonstrated that miR-652 was downregulated in ESCC tissues and cell lines. Functional assays showed that upregulation of miR-652 expression decreased proliferation and invasion of ESCC cells. Mechanistically, fibroblast growth factor receptor 1 (FGFR1) was determined to be a direct target of miR-652 in ESCC cells. Additionally, FGFR1 was upregulated in ESCC tissues, and the expression of FGFR1 was inversely correlated with miR-652 expression. Furthermore, restoring FGFR1 expression abolished the suppressive effects of miR-652 overexpression on the proliferation and invasion of ESCC cells. These findings demonstrated that miR-652 inhibits the proliferation and invasion of ESCC cells by directly targeting FGFR1.

Identification of lung-adenocarcinoma-related long non-coding RNAs by random walking on a competing endogenous RNA network.

BACKGROUND: Identification of novel risk long non-coding RNAs (lncRNAs) in lung adenocarcinoma (LUAD) is still a significant challenge in cancer research. METHODS: In this study, we first constructed a LUAD-specific competing endogenous RNA (ceRNA) network using both experimental- and computational-supported datasets. Then, a random walking with restart method was performed to predict LUAD-associated risk lncRNAs based on the ceRNA network. The role of lncRNA MAPKAPK5-AS1 was assessed by siRNA transfection, followed by a colony formation assay, the CCK-8 assay, and immunofluorescence on A549 cells. RESULTS: Our method achieved an area under the curve (AUC) value of over 0.83. Of the several potential novel LUAD-related lncRNAs identified, the highest ranked lncRNA was SNHG12, which, interestingly, was also shown to promote tumorigenesis and metastasis in LUAD in a recent study. Furthermore, we found that the expression of MAPKAPK5-AS1, which was ranked second, was higher in both LUAD tissues and three LUAD cell lines. After the silencing of MAPKAPK5-AS1 by siRNA transfection, a colony formation assay revealed fewer colonies, and a CCK-8 assay revealed significantly suppressed growth of A549 cells. Moreover, immunofluorescence staining of Ki-67, a proliferation marker, revealed that the proliferation capability of A549 was dramatically reduced following MAPKAPK5-AS1 downregulation. AO/EB staining showed an increased proportion of apoptotic cells among A549 cells depleted of MAPKAPK5-AS1. CONCLUSIONS: In brief, the lncRNAs were predicted to serve as potential biomarkers for the diagnosis, treatment, and prognosis of LUAD.

Risk factors of atrial fibrillation occurring after radical surgery of esophageal carcinoma.

BACKGROUND: Atrial fibrillation (AF) is a common complication after radical surgery of esophageal cancer. The aim of this study was to explore AF risk factors after radical surgery of esophageal carcinoma. METHOD: The data of 335 patients with esophageal cancer who were admitted in our hospital from January 2014 to August 2016 for the first time were retrospectively analyzed. We retrieved the papers in some data banks using the search terms including English and Chinese search terms, and obtained 13 factors which were mentioned in more than 6 papers. The 13 factors including age, gender, history of smoking, history of hypertension, history of peripheral vascular disease, history of cardiac stents or angina pectoris, preoperative pulmonary infection, preoperative brain natriuretic peptide (BNP) level, preoperative left ventricular diastolic dysfunction, operative method, lesion location, intraoperative blood transfusion, adhesion between lymph nodes and pericardium, underwent univariate and multivariate analyses. RESULTS: Of the 335 patients with esophageal cancer, 48 had AF within one week after operation. Univariate analysis indicated that the age (OR: 4.89; CI: 2.53-9.47, P: 0.000), gender (OR: 2.26; CI: 1.17-4.37, P: 0.013), history of peripheral vascular disease (OR: 2.29; CI: 1.06-4.92, P: 0.030), history of cardiac stents or angina pectoris (OR: 27.30; CI: 12.44-59.91, P: 0.000), preoperative BNP level (OR: 27.13; CI: 10.97-67.06, P: 0.000), preoperative left ventricular diastolic dysfunction (OR: 2.22; CI: 1.19-4.14, P: 0.012), operative method (OR: 2.09; CI: 1.002-4.380, P: 0.046), intraoperative blood transfusion (OR: 20.24; CI: 8.39-48.82, P: 0.000), and adhesion between lymph nodes and pericardium were risk factors (OR: 2.05; CI: 1.08-3.87, P: 0.024). Furthermore, multivariate analysis displayed that advanced age (OR: 5.044; CI: 1.748-14.554, P: 0.003), male (OR: 6.161; CI: 2.143-17.715, P: 0.001), history of cardiac stents or angina pectoris (OR: 48.813; CI: 13.674-174.246, P: 0.000), preoperative BNP > 100 (OR: 41.515; CI: 9.380-183.732, P: 0.000), open surgery (OR: 3.357; CI: 1.026-10.983, P: 0.045), intraoperative blood transfusion (OR: 58.404; CI: 10.777-316.509, P: 0.000), and adhesion between lymph nodes and pericardium (OR: 3.954; CI: 1.364-11.459, P: 0.011) were risk factors which could increase the incidence of postoperative AF. CONCLUSION: We should pay attention to the above risk factors in order to reduce the incidence of postoperative AF.

Identification of potential microRNAs and their targets in promoting gefitinib resistance by integrative network analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for about 80-85% of lung cancers. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib are considered the best choice for first-line treatment for the patients with NSCLC harboring EGFR-activating alterations. Nonetheless, 10-30% of patients may not obtain an objective response and may also experience rapid progression. The aim of our research, based on the integrative bioinformatics review, was to identify the possible miRNAs involved in gefitinib resistance. METHOD: A gefitinib-resistant network composed of 15 miRNAs and 34 targets were constructed by using the bioinformatics analyses of three microarray datasets. Of these miRNAs, effects of miR-342-3p on gefitinib resistance were investigated on a gefitinib-resistant cell model (A549/GR and PC/GR cells). RESULTS: We reported that over-expression of miR-342-3p could significantly increase the resistance to gefitinib of A549/GR and PC9/GR cells and vice versa. Then, we recognized CPA4 as a target of hsa-miR-342-3p by a luciferase reporter assay. The increase in hsa-miR-342-3p levels led to a significant reduction in CPA4 protein expression. However, the opposite results were observed upon miR-342-3p knockdown. Finally, we found that enforced CPA4 expression partially reversed miR-342-3p effects in A549/GR cells. CONCLUSIONS: Collectively, these findings suggest that the upregulation of miR-342-3p contributes to gefitinib resistance by targeting CPA4, which may serve as a potential treatment option to overcome gefitinib resistance in patients with NSCLC.

Expression and Effects of Long Non-Coding RNA, LINC01124, in Non-Small Cell Lung Cancer.

OBJECTIVE: To investigate the expression and evaluate the clinical significance of long non-coding RNA, LINC01124, in non-small cell lung cancer (NSCLC) and to study its influence in this tumor. METHODS: Hundred specimens of NSCLC tissues and normal lung tissues after surgery were collected. The qRT-PCR for LINC01124 expression was performed on cancerous and normal lung tissues. The correlations between the expression of LINC01124 and pathological characteristics were analyzed. PcDNA-LINC01124 was transfected to upregulate LINC01124 expression in NSCLC cells, and the transfection efficiency was evaluated by the qRT-PCR. CCK8 assay, wound-healing assay, and the Transwell assay were performed to evaluate the effect of ectopic LINC01124 expression on proliferation, migration, and invasive of NSCLC cells. RESULTS: The expression level of LINC01124 was downregulated in tumor tissues when compared with the paired normal lung tissues (P<0.05). The expression of LINC01124 was associated with patients' age and distant metastasis (P<0.05). Enforced expression of LINC01124 significantly inhibited the proliferation, migration, and invasive ability of NSCLC cells. CONCLUSION: The expression of LINC01124 was decreased in patients with NSCLC of older age and with those having distant metastasis. LINC01124 may inhibit cell proliferation, migration, and invasive ability.

Long non-coding RNA LINC00222 regulates GSK3ß activity and promotes cell apoptosis in lung adenocarcinoma.

Recent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulating cellular processes such as differentiation, proliferation, metastasis and apoptosis. These lncRNAs are found to be dysregulated in a variety of cancers. However, the underlying mechanisms of lncRNAs action in lung adenocarcinoma remain unclear. We investigated expression of the lncRNA LINC00222 in 76 lung adenocarcinoma tissues and paired normal lung tissues and found that LINC00222 is downregulated in lung adenocarcinoma tissues. Enforced expression of LINC00222 significantly inhibited the proliferation, migration and invasive ability of lung adenocarcinoma cells, and also induced apoptosis. Furthermore, overexpression of LINC00222 enhanced the activity of glycogen synthase kinase-3ß (GSK3ß), which is a key element of the Wnt signaling pathway. Taken together, our findings suggest that LINC00222 acts as a tumor suppressor in lung adenocarcinoma and, therefore, could serve as a valuable prognostic biomarker and therapeutic target for lung adenocarcinoma patients.

The long non-coding RNA MIAT regulates zinc finger E-box binding homeobox 1 expression by sponging miR-150 and promoteing cell invasion in non-small-cell lung cancer.

The myocardial infarction associated transcript (MIAT), a long non-coding RNA (lncRNA), was originally identified as a candidate gene for myocardial infarction, and was recently shown to participate in the progression of cancer and the process of metastasis. However, the biological role of MIAT and the underlying mechanisms that mediate its role in non-small-cell lung cancer (NSCLC) remain unclear. Here, we have shown that the expression of MIAT in NSCLC tissues was upregulated. Knockdown of MIAT substantially inhibited the invasive ability of NSCLC cells. Moreover, the knockdown of MIAT significantly downregulated the expression of the zinc finger E-box binding homeobox 1 (ZEB1), that was upregulated in NSCLC and that promoted cell invasion. Rather than by direct interactions, we found that MIAT indirectly regulated ZEB1 expression through sponging and suppressing microRNA (miR)-150, which represses ZEB1 and interacts with MIAT in a sequence-specific manner. Thus, MIAT may inhibit ZEB1 expression and promote cell invasion of NSCLC cells via the miR-150/ZEB1 pathway. Taken together, our findings suggested that MIAT plays an oncogenic role in NSCLC through the ZEB1 signaling pathway by sponging miR-150, and MIAT may therefore serve as a valuable prognostic biomarker and therapeutic target for NSCLC.

Knockdown of GluA2 induces apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway.

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are important glutamatergic receptors that mediate fast excitatory synaptic transmission in the brain. Previous studies have demonstrated that glutamate ionotropic receptor AMPA type subunit 2 (GluA2), one of the four subunits that comprise AMPA receptors, is a potential novel marker for poor prognosis in patients with human lung cancer. However, the mechanisms of GluA2-induced apoptosis, proliferation and migration in lung cancer remain unknown. The present study aimed to explore the mechanisms underlying these effects of GluA2 in human lung cancer by silencing GluA2 in A549 cells. Using the Cell Counting Kit-8 assay, western blot analysis and acridine orange/ethidium bromide staining, downregulation of GluA2 was revealed to significantly inhibit the proliferation and significantly promote the apoptosis of A549 cells. Knockdown of GluA2 was also revealed to be associated with increased caspase-3 activity, increased Bcl-2-associated X protein and Bcl-2-associated death promoter (Bad) expression, and decreased expression of B-cell lymphoma-2, p-Bad and X-linked inhibitor of apoptosis protein. In addition, GluA2 silencing upregulated cellular tumor antigen p53 (p53)/p21Cip1/Waf1/p16INK4a protein. In conclusion, these results indicate that the effects of GluA2 in lung cancer are mediated by the caspase-3 and p53/p21Cip1/Waf1/p16INK4a signaling pathways. Therefore, GluA2 may be a potential novel therapeutic target for the treatment of lung cancer.

Long non-coding RNA SNHG1 regulates zinc finger E-box binding homeobox 1 expression by interacting with TAp63 and promotes cell metastasis and invasion in Lung squamous cell carcinoma.

The long non-coding RNAs (lncRNAs) have been recently shown to participate in the progression of a variety of cancers. However, the biological role of lncRNAs and the underlying mechanisms in Lung squamous cell carcinoma (SCC) or lung adenocarcinoma (AD) remain unclear. Herein, we investigated expression of 5 lncRNAS (SNHG1, NCBP2-AS2, LINC01206, SOX2-OT and LINC01419) in SCC and AD tissues. SNHG1 was one of over-expressed lncRNAs in SCC tissues. Knockdown of SNHG1 significantly inhibited the proliferation, metastasis, invasive ability and induced apoptosis of SCC cells. Moreover, SNHG1 affected the expression of zinc finger E-box binding homeobox 1(ZEB1), which has also been observed to be up-regulated in SCC and to promote cell metastasis and invasion. Rather than direct interaction, SNHG1 regulated ZEB1expression by suppressing the activity of p63 TA isoform (TAp63), which is a repressor of ZEB1 and physically associates with SNHG1. Furthermore, SNHG1 promoted ZEB1 expression and promoted cell proliferation, metastasis, invasive but inhibited apoptosis of SCC cells via the TAp63/ZEB1 pathway. Taken together, our findings suggested that SNHG1 might play an oncogenic role in SCC through ZEB1 signaling pathway by inhibiting TAp63 and might serve as a valuable prognostic biomarker and therapeutic target for SCC patients.

The feasibility and advantage of uniportal video-assisted thoracoscopic surgery (VATS) in pulmonary lobectomy.

BACKGROUND: Ongoing improvements in technique and instruments for video-assisted thoracoscopic surgery (VATS) have made minimally-invasive uniportal VATS lobectomy a reality. However, the outcomes of the procedure are still under investigation, and at present, uniportal VATS lobectomy is performed infrequently at most hospitals. We have therefore reviewed our outcomes with this procedure in an attempt to validate its safety, efficacy, and feasibility. METHODS: We retrospectively analyzed and compared perioperative data for patients who underwent uniportal, two-port, and traditional three-port VATS lobectomy between January 2015 and December 2015 at our hospital. RESULTS: Among 257 patients who had successful VATS lobectomy during the study period, 73 underwent uniportal VATS, 86 underwent two-port VATS, and 98 underwent traditional three-port VATS. There were no surgical or 30-day postoperative mortalities, and no significant differences in operative times, blood loss, number of lymph nodes retrieved and nodal stations explored, drainage times, length of hospital stay, or postoperative complications among the three groups. The visual analogue scale (VAS) pain scores were significantly lower in the uniportal VATS group after surgery (P < 0.05). CONCLUSIONS: Uniportal VATS lobectomy is a safe and feasible surgical procedure that is associated with decreased surgical trauma and less postoperative pain compared to traditional VATS. Further long term follow-up analyses in large numbers of patients are ongoing.

Alpinetin inhibits lung cancer progression and elevates sensitization drug-resistant lung cancer cells to cis-diammined dichloridoplatium.

OBJECTIVE: Alpinetin is a novel flavonoid that has demonstrated potent antitumor activity in previous studies. However, the efficacy and mechanism of alpinetin in treating lung cancer have not been determined. METHODS: We evaluated the impact of different doses and durations of alpinetin treatment on the cell proliferation, the apoptosis of lung cancer cells, as well as the drug-resistant lung cancer cells. RESULTS: This study showed that the alpinetin inhibited the cell proliferation, enhanced the apoptosis, and inhibited the PI3K/Akt signaling in lung cancer cells. Moreover, alpinetin significantly increased the sensitivity of drug-resistant lung cancer cells to the chemotherapeutic effect of cis-diammined dichloridoplatium. Taken together, this study demonstrated that alpinetin significantly suppressed the development of human lung cancer possibly by influencing mitochondria and the PI3K/Akt signaling pathway and sensitized drug-resistant lung cancer cells. CONCLUSION: Alpinetin may be used as a potential compound for combinatorial therapy or as a complement to other chemotherapeutic agents when multiple lines of treatments have failed to reduce lung cancer.

Loss of RhoA expression prevents proliferation and metastasis of SPCA1 lung cancer cells in vitro.

Lung cancer is the leading cause of cancer-related death worldwide, mainly due to its highly metastatic properties. Previously, we reported an inverse correlation between Rho-kinase inhibitor and the progression of the lung cancer cells. The purpose of this study was to investigate the effects of RhoA on the proliferation, adhesion, invasion, and migration of SPCA1 lung carcinoma cells and to explore the underlying molecular mechanisms. RNA interference was used to downregulate RhoA expression in these cells. Through G418 screening, we generated SPCA1 lung cancer cell lines with stable RhoA silencing. We then observed the cell behaviour, and used matrix metalloproteinase (MMP) activity and western blot assays to evaluate the underlying molecular mechanisms. The proliferation, adhesion, migration, and invasion of SPCA1 lung cancer cells were decreased after knockdown of RhoA. At the molecular level, the total amounts of active MMP2 and MMP9 were decreased by about 17.21% (P<0.05) and 45.32% (P<0.01), respectively. Myosin phosphatase targeting subunit 1 phosphorylation (P-MYPT1) was reduced by 36.16% (P<0.05). Taken together, our findings show that the knockdown of RhoA prevents proliferation and metastasis in SPCA1 lung cancer cells. Changes in MMP2, MMP9, and P-MYPT1 levels and activity might be some of the molecular mechanisms underlying these effects.

The Rho-kinase inhibitor inhibits proliferation and metastasis of small cell lung cancer.

The purpose of this study was to investigate the effects of Rho-kinase inhibitor on the growth, proliferation, apoptosis, adhesion, invasion and migration of NCI-H446 small cell lung cancer cells and to explore the underlying molecular mechanisms involved in this process. After treatment to NCI-H446 small cell lung cancer cells with Fasudil, a Rho-kinase inhibitor, cell biological behaviors were observed. Matrix metalloproteinase activity and Western blot assay were used to evaluate underlying molecular mechanisms. The IC50 of Fasudil to NCI-H446 small cell lung cancer cells was approximately 0.86 mg/ml (95% confidence limits: 0.65-1.17 mg/ml). After treatment with 0.75 mg/ml Fasudil, the ability of NCI-H446 small cell lung cancer cells, including growth, proliferation, adhesion, migration, and invasion were decreased, while their apoptosis was increased significantly. On the molecular level, the total amounts of active MMP2 and MMP9 were decreased about 20.5% (P<0.05) and 57.5% (P<0.01) respectively. Myosin phosphatase targeting subunit 1 phosphorylation (P-MYPT1) was reduced by 27.9% (P<0.05). The activation of caspase-3, and PARP cleavage in experimental group were significantly higher than those in normal control group (P<0.01). Meanwhile, treatment with Fasudil led to a remarkable reduction of the phosphorylated STAT3 (P-STAT3) (P<0.01). Taken together, our findings show that Fasudil prevents the growth, metastasis and induces apoptosis of NCI-H446 small cell lung cancer cells by inhibiting the Rho/Rho-kinase pathway. Changes in MMP2, MMP9, P-MYPT1, caspase-3, PARP cleavage and P-STAT3 may be one of its molecular mechanisms.