Long non-coding RNA FLVCR1-AS1 contributes to the proliferation and invasion of lung cancer by sponging miR-573 to upregulate the expression of E2F transcription factor 3.

Lung cancer is one of the most common causes of cancer-related death all over the world. In recent years, long non-coding RNAs (lncRNAs) have been reported to play critical roles in the development and progression of human malignancies. In the present study, we aimed to study the role and mechanism of FLVCR1-AS1 in human non-small cell lung cancer (NSCLC). Results revealed that FLVCR1-AS1 was markedly upregulated in NSCLC tissues and cell lines. Knockdown of FLVCR1-AS1 significantly inhibited the proliferation, migration, invasion and promoted apoptosis of NSCLC cells, and suppressed tumor growth of NSCLC in vivo. Moreover, we explored regulatory mechanism, and found that FLVCR1-AS1 functioned as a competing endogenous RNA (ceRNA) by directly binding to miRNA-573, and E2F transcription factor 3 (E2F3) was identified as a down-stream target of miR-573. FLVCR1-AS1 positively regulated E2F3 expression through inhibiting miR-573 in NSCLC cells. Our findings suggested that FLVCR1-AS1/miR-573/E2F3 axis was an important signaling pathway in mediating tumorigenesis and progression of NSCLC, and further indicated that FLVCR1-AS1 could be a novel diagnostic biomarker and therapeutic target for NSCLC.

SNHG3 Knockdown Suppresses Proliferation, Migration and Invasion, and Promotes Apoptosis in Non-Small Cell Lung Cancer Through Regulating miR-216a/ZEB1 Axis.

BACKGROUND: Tumour growth and development are dependent on many factors including long noncoding RNAs (lncRNAs). However, limited information is available on the involvement of lncRNAs in non-small cell lung cancer (NSCLC) and the molecular mechanisms have not been defined. Here, we examined the expression of small nucleolar RNA host gene 3 (SNHG3) and its contribution to the development of NSCLC. METHODS: We detected SNHG3, miR-216a, and ZEB1 expression in tissues from NSCLC patients and lung adenocarcinoma cell lines using quantitative real-time polymerase chain reaction. Proliferation, migrations, invasion, and apoptosis of tumour cells were assessed using cell counting kit-8, transwell experiments, and flow cytometry after SNHG3 knockdown by small interfering RNAs. Bioinformatics and luciferase reporter assays were employed for analysing the interactions between SNHG3, miR-216a, and ZEB1. RESULTS: We found highly upregulated SNHG3 in tissues and cells from NSCLC patients, which was linked to poor prognosis. SNHG3 silencing diminished the ability of NSCLC cells to proliferate, migrate, and invade and promoted apoptosis. Furthermore, SNHG3 competed with endogenous RNA and enhanced the expression of ZEB1 by interfering with miR-216a. ZEB1 overexpression or miR-216a blockade reversed SNHG3-induced tumour inhibition. Similar effects were observed in vivo where SNHG3 knockdown inhibited NSCLC tumour growth by reducing expression of miR-216a while increasing that of ZEB1. CONCLUSION: Knockdown of SNHG3 inhibits NSCLC tumour development and progression by upregulation of ZEB1 and interference with miR-216a, revealing an attractive alternative target for patients with NSCLC.

Restoration of miR-26b expression partially reverses the cisplatin resistance of NSCLC by targeting tafazzin.

BACKGROUND: Dysregulation of microRNAs has been reported to be responsible for drug resistance of cancers. However, the association between aberrant expression of miR-26b and cisplatin resistance in non-small cell lung cancer (NSCLC) remains unclear. METHODS: PC9 and A549 were used to establish the cisplatin resistance models on NSCLC. Expression of miR-26b in cisplatin-resistant PC9 and A549 cells (PC9/R and A549/R) was detected by quantitative real-time PCR assays. Drug sensitivity and mitochondrial apoptosis were detected by Cell Counting Kit-8 assay and flow cytometry assay, respectively. The target relationship between miR-26b and tafazzin (TAZ) was validated by dual-luciferase reporter assay. RESULTS: Obvious downregulation of miR-26b was observed in PC9/R and A549/R cells. Restoration of miR-26b partially reversed the cisplatin resistance of PC9/R and A549/R cells. Expression of TAZ was increased in PC9/R and A549/R cells compared to the parental PC9 and A549 cells. Results of dual-luciferase reporter assays verified that TAZ was targeted by miR-26b. We showed that restoration of miR-26b expression inhibited the TAZ expression and thus expanded the mitochondrial pathway of apoptosis induced by cisplatin in PC9/R and A549/R cells. CONCLUSION: Restoration of miR-26b expression partially reverses the cisplatin resistance of NSCLC by targeting TAZ. miR-26b/TAZ axis may represent a potential strategy to reverse the cisplatin in NSCLC.

Erratum: MicroRNA-137 inhibits cell migration and invasion by targeting bone morphogenetic protein-7 (BMP7) in non-small cell lung cancer cells.

[This corrects the article on p. 10847 in vol. 8, PMID: 26617798.].

MicroRNA-383-5p acts as a prognostic marker and inhibitor of cell proliferation in lung adenocarcinoma by cancerous inhibitor of protein phosphatase 2A.

Lung cancer is the leading cause of cancer-associated mortality worldwide. MicroRNAs (miRNAs/miRs) serve a role in the occurrence and development of lung cancer. The aim of the present study was to analyze the expression and function of the proliferation-associated miR-383-5p in lung adenocarcinoma (LAC). Samples of human LAC and matched adjacent normal lung tissues were surgically removed, and miR-383-5p expression and the pathological characteristics of lung adenocarcinoma were investigated. The present study revealed that miR-383-5p expression level was significantly decreased in LAC tissues and its expression levels were markedly associated with tumor size and differentiation. Overexpression of miR-383-5p in A549 and H1299 LAC cell lines inhibited cell proliferation by G1 cell cycle phase arrest and induction of apoptosis. Cancerous inhibitor of protein phosphatase 2A (CIP2A), a potential target gene of miR-383-5p, was inversely associated with miR-383-5p expression level in LAC tissues and cell lines. Furthermore, the results of the present study demonstrated that CIP2A was directly regulated by miR-383-5p and the restoration of CIP2A expression reversed the inhibitory effects of miR-383-5p on LAC cell proliferation. In conclusion, the results of the present study demonstrated that miR-383-5p was downregulated in LAC tissues. By targeting CIP2A, miR-383-5p exerts its anti-proliferative function in LAC, suggesting its use a potential novel potential prognostic biomarker and therapeutic target for LAC.

In silico insight into EGFR treatment in patients with lung carcinoma and T790M mutations.

The T790M mutational basis of treatment failure, following treatment via alteration of the epidermal growth factor receptor (EGFR) pathway, is a well-known anomaly in patients with non-small cell lung cancer (NSCLC). The T790M mutation activates the kinase domain, causing tyrosine kinase inhibitors, such as gefitinib, to elicit little or no response. To overcome this acquired resistance in NSCLC cells, the present study utilized a structure-based drug designing method to identify a novel lead compound. An in-house traditional Chinese medicinal compound database was used and following initial virtual screening, pre-absorption, distribution, metabolism and excretion/Tox and automated docking analyses, nardosinon was selected as the most appropriate candidate for further analysis. Two NSCLC cell lines, PC9GR4 and H2347, were used to test nardosinon and the results were compared with gefitinib. Results from an initial cell death assay revealed that nardosinon was able to induce cell death in NSCLC cells with and without the T790M mutation. These findings suggest that nardosinon may be an effective pharmacological compound for NSCLC treatment, including T790M EGFR mutant NSCLC cells.

MicroRNA-137 inhibits cell migration and invasion by targeting bone morphogenetic protein-7 (BMP7) in non-small cell lung cancer cells.

MicroRNA-137 (miR-137) was reported to be dysregulated in several human cancers. However, the function and mechanism of miR-137 in non-small cell lung cancer (NSCLC) is still unclear. In the current study, we explored the role of miR-137 in NSCLC progression. Using qRT-PCR, our data showed that miR-137 was significantly down-regulated in NSCLC tissues and cell lines. In vitro functional assay, we found that over-expression of miR-137 suppressed NSCLC cells proliferation, migration and invasion, indicating that miR-137 could act as a tumor suppressor in NSCLC progression. In addition, bone morphogenetic protein-7 (BMP7) was identified as a target of miR-137 in NSCLC cells, Luciferase reporter assay suggested that miR-137 directly targeted 3'-UTR of BMP7, and correlation analysis revealed that BMP7 inversely correlated with miR-137 in NSCLC tissues. Furthermore, Restoration of BMP7 remarkably reversed the tumor suppressive effects of miR-137 on NSCLC cell proliferation, migration, and invasion. Taken together, our findings suggested that miR-137/BMP7 axis could contribute to the progression of NSCLC, suggesting miR-137 as a potential therapeutic target for the treatment of NSCLC.

Annexin A11 (ANXA11) gene polymorphisms are associated with sarcoidosis in a Han Chinese population: a case-control study.

OBJECTIVES: To further identify the single-nucleotide polymorphisms (SNPs) that contribute to the genetic susceptibility to sarcoidosis, we examined the potential association between sarcoidosis and 15 SNPs of the ANXA11 gene. DESIGN: A case-control study. SETTING: A tuberculosis unit in a hospital of the university in China. PARTICIPANTS: Participants included 412 patients with sarcoidosis and 418 healthy controls. METHODS: The selected SNPs were genotyped using the MALDI-TOF in the MassARRAY system. RESULTS: Statistically significant differences were found in the allelic or genotypic frequencies of the rs2789679, rs1049550 and rs2819941 in the ANXA11 gene between patients with sarcoidosis and controls. The rs2789679 A allele (p=0.00004, OR=1.42, 95% CI 1.17 to 1.73) and rs2819941 T allele (p=0.0006, OR=1.41, 95% CI 1.16 to 1.71) were significantly more frequent in patients with sarcoidosis compared with controls. The frequency of the rs1049550 T allele (p=0.000002, OR=0.61, 95% CI 0.49 to 0.74) in patients with sarcoidosis was significantly lower than that in controls. The multi-SNP model reveals that rs1049550 is the only independent SNP association effect after accounting for the other two marginally associated SNPs. In block 2 (rs1049550-rs2573351), the T-C haplotype occurred significantly less frequently (p=0.001), whereas the C-C haplotypes occurred more frequently (p=0.0001) in patients with sarcoidosis than controls. Furthermore, genotype frequency distribution revealed that, in rs1049550, the CC genotype was significantly more in patients with chest X-ray (CXR) stage I sarcoidosis than in patients with CXR stage II-IV sarcoidosis (p=0.012). CONCLUSIONS: These findings point to a role for the polymorphisms of ANXA11 in sarcoidosis in a Chinese Han population, and may be informative for future genetic studies on sarcoidosis.

Increased expression of the lncRNA PVT1 promotes tumorigenesis in non-small cell lung cancer.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the major cause of cancer death worldwide. Increasing evidence shows that long non coding RNAs (lncRNAs) are widely involved in the development and progression of NSCLC. lncRNA PVT1 in several cancers has been studied, its role in lung cancer remains unknown. Our studies were designed to investigate the expression, biological role and clinical significance of PVT1 in lung cancer. METHODS: lncRNA PVT1 expression in 82 NSCLC tissues and 3 lung cancer cell lines was measured by quantitative Real-time PCR (qRT-PCR). Its association with overall survival of patients was analyzed by statistical analysis. RNA interference (RNAi) approaches were used to investigate the biological functions of PVT1. The effect of PVT1 on proliferation was evaluated by MTT, cell migration and invasion ability was evaluated by cell migration and invasion assays. RESULTS: lncRNA PVT1 expression was significantly upregulated in NSCLC tissues and lung cancer cells when compared with corresponding adjacent normal tissues and normal bronchial epithelial cells. Increased PVT1 expression was significantly correlated with histological grade and lymph node metastasis. In addition, NSCLC patients with PVT1 higher expression have shown significantly poorer overall survival than those with lower PVT1 expression. And PVT1 expression was an independent prognostic marker of overall survival in a multivariate analysis. In vitro assays our results indicated that knockdown of PVT1 inhibited cell proliferation, migration, and invasion. CONCLUSIONS: Our data indicated that lncRNA PVT1 is significantly upregulated in NSCLC tissues and may represent a new biomarker and a potential therapeutic target for NSCLC intervention.