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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 (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.

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., Overexpression of miR‐338 significantly inhibited the proliferation and epithelial‐mesenchymal transition of non‐small‐cell lung cancer (NSCLC) cell. Moreover introduction of nuclear factor of activated T cells c1 (NFATc1) reversed the inhibitory effects of miR‐338 overexpression. Therefore, our outcomes showed critical roles for miR‐338/ NFATc1 axis in the pathogenesis of NSCLC and suggested its possible application in tumor treatment.

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.

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.

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.

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-3β (GSK3β), 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.

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

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

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.

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