Investigation of LINC00342 as a poor prognostic biomarker for human patients with non-small cell lung cancer.

Cyclic long noncoding RNAs have recently become major players in cancer biology and can serve as biomarkers for cancer diagnosis and prognosis, and as potential therapeutic targets. We explored circulating LINC00342 as a predictor of non-small cell lung cancer (NSCLC). The expression of LINC00342 in tissues, serum, PBMC, and NSCLC cell lines were screened by reverse transcription quantitative polymerase chain reaction. A multistage validation and risk score formula detection analysis was used. The effect of LINC00342 on proliferation was assessed by MTT, p53, and PTEN pathways, which were analyzed by Western blot analysis. We found that LINC00342 was upregulated in the tissues, serum, and PBMC of patients with NSCLC. In addition, patients with higher LINC00342 expression levels were associated with poor overall survival. For the diagnosis of NSCLC, the specificity and sensitivity of LINC00342 were significantly higher than that of CYFRA 21-1. Moreover, LINC00342 promoted proliferation by inhibiting the expression of p53 and PTEN proteins in NSCLC cell lines. Our study demonstrates that LINC00342 is involved in the development, and LINC00342 may be a potential diagnostic factor and a target for new therapies for future patients with NSCLC.

linc00968 inhibits the tumorigenesis and metastasis of lung adenocarcinoma via serving as a ceRNA against miR-9-5p and increasing CPEB3.

Increasing evidence confirms that long noncoding RNAs (lncRNAs) exert vital functions in multiple biological process among malignant cancers. In the current study, we uncovered that linc00968 was downregulated in lung adenocarcinoma (LUAD). Furthermore, the low level of linc00968 was correlated with worse prognosis in patients with LUAD. Upregulation of linc00968 restrained the growth and metastatic phenotypes of LUAD cell in vitro and in vivo. Using bioinformation methods and luciferase reporter assay, we identified that linc00968 acted as a competing endogenous RNA (ceRNA) via sponging miR-9-5p to modulate the level of Cytoplasmic Polyadenylation Element Binding Protein 3 (CPEB3) in LUAD. In addition, LUAD cell migration, colony formation and epithelial-mesenchymal transition (EMT) process were suppressed by linc00968 while these aggressive traits were reversed by miR-142-5p or CPEB3 silencing. Altogether, our work disclosed that linc00968 played a critical role in LUAD and linc00968/miR-9-5p/CPEB3 regulatory axis might be a potential treatment target in LUAD.

Linc00221 modulates cisplatin resistance in non-small-cell lung cancer via sponging miR-519a.

Cisplatin resistance has been long considered an obstacle to the efficacy of chemotherapy in non-small-cell lung cancer (NSCLC). Long non-coding RNAs (lncRNAs) have been widely reported to participate in the various biological process including cancer. In the present study, we aim to explore the functions of Linc00221 and miR-519a in the sensitivity and the resistance of NSCLC to cisplatin. The levels of Linc00221, miR-519a, and zinc finger and BTB domain-containing five (ZBTB5) in NSCLC tissues were detected by qRT-PCR and Western blot. Colony formation and MTT assays were applied to detect the viability of cells after cisplatin treatment. Dual luciferase reporter assays were used to detect the inhibitory effect of miR-519a on ZBTB5 and Linc00221, and pull down experiments were employed to determine the direct interaction between Linc00221 and miR-519a. Our results showed that Linc00221 was highly expressed in cisplatin-resistant NSCLC tissues and cells and closely associated with poor prognosis. Linc00221 promoted the cisplatin resistance of NSCLC and miR-519a was a direct target of Linc00221. In addition, miR-519a could promote cisplatin sensitivity in NSCLC cells by targeting ZBTB5. Linc00221 could mediate the cisplatin sensitivity in NSCLC by adsorbing miR-519a to prevent its down-regulation of ZBTB5. In conclusion, Linc00221 promotes cisplatin resistance in NSCLC through the downstream miR-519a/ZBTB5 signaling axis, which could be used as a potential diagnostic and therapeutic target for clinical cisplatin-resistant NSCLC patients.

miR­505 inhibits cell growth and EMT by targeting MAP3K3 through the AKT­NFκB pathway in NSCLC cells.

MicroRNAs (miRNAs) are short non­coding RNAs, which generally regulate gene expression at the post­transcriptional level. Dysregulation of miRNAs has been reported in numerous cancer types, including lung cancer. In the present study, the role of miR­505 in non­small cell lung cancer (NSCLC) cells was investigated. miR­505 served a tumor suppressor role in NSCLC cells. By reverse transcriptase­quantitative polymerase chain reaction detection, it was demonstrated that miR­505 was downregulated in NSCLC tissues and cell lines, which is negatively associated with large tumor size, Tumor­Node­Metastasis stage and distant metastasis in patients with NSCLC. Functional studies revealed that miR­505 inhibited cell proliferation, migration, invasion and epithelial­mesenchymal transition progress in vitro and tumor growth in vivo. Mechanically, mitogen­activated protein kinase kinase kinase 3 (MAP3K3) was identified as a direct target of miR­505 by binding to its 3'untranslated region and demonstrated to mediate the tumor suppressor roles of miR­505 in NSCLC cells. The effect of miR­505 on the activation of AKT/nuclear factor­κB (NFκB) pathway, which was downstream targets of MAP3K3, was further analyzed by western blot analysis and immunofluorescence analyses. The data demonstrated the inhibition of the AKT/NFκB pathway upon overexpressing miR­505 and the activation of AKT/NFκB pathway upon silencing miR­505. Collectively, the data revealed the novel role and target of miR­505 in NSCLC cells, which may provide novel insights regarding its role in the carcinogenesis of NSCLC and its potential values for clinical applications.

Efficacy and safety of weekly intravenous nanoparticle albumin-bound paclitaxel for non-small cell lung cancer patients who have failed at least two prior systemic treatments.

BACKGROUND: The study was conducted to evaluate the efficacy and safety of weekly intravenous nanoparticle albumin-bound paclitaxel (NAB-paclitaxel) treatment in patients with advanced non-small-cell lung cancer (NSCLC) who have undergone multi-line therapy, and to investigate the association of secreted protein acidic and rich in cysteine (SPARC) expression status with clinical outcome. METHODS: Sixty-four patients who received NAB-paclitaxel treatment (130 mg/m2 on days 1 and 8 of a 21 day cycle) as third line or further systemic treatment from 1 May 2011 to 30 June 2014 were included in this retrospective analysis. Tumor tissue was available in 28 patients for analysis of SPARC expression by immunohistochemistry. RESULTS: Sixty-two patients had response evaluation and complete survival follow-up data; 83.9% received the weekly NAB-paclitaxel as fourth-line treatment or beyond. The objective response and disease control rates (n = 62) were 16.1% (10/62) and 64.5% (40/62), respectively. The median progression-free and overall survival rates were 3.7 (95% confidence interval 2.6-4.8) and 9.8 months (95% confidence interval 6.9-12.8), respectively. Previous treatment with taxane did not affect the response to NAB-paclitaxel. The main grade 3-4 toxicities experienced were neutropenia (9.4%) and leukopenia (7.8%). Patients with SPARC expression in tumor stroma but not in cancer cells had poorer progression-free survival compared with those with negative SPARC expression in tumor stroma cells (3.3 vs. 5.0 months, P = 0.036). CONCLUSION: Weekly NAB-paclitaxel might be effective for heavily pretreated NSCLC patients. SPARC expression in tumor stroma cells might be a potential negative predictor of NAB-paclitaxel.

Primary signet-ring cell carcinoma of the lung treated with crizotinib: A case report.

Primary signet-ring cell adenocarcinoma (SRCA) of the lung is an extremely rare subtype of lung adenocarcinoma with a poor prognosis. The presence of an SRC component is considered to be a prominent clinicopathological characteristic of EML4-ALK-positive non-small cell lung cancer (NSCLC). Crizotinib, an anaplastic lymphoma kinase inhibitor, has been approved for the treatment of EML4-ALK NSCLC by previous studies, but its effect on SRCA, an extremely rare subtype of lung adenocarcinoma, has yet to be elucidated. Therefore, the present study aimed to evaluate the clinical response of SRCA to crizotinib, and examine the potential use of crizotinib as a treatment for the carcinoma. A 43-year-old male was admitted to the Qingdao Municipal Hospital (Qingdao, China) with dyspnea. Chest computed tomography (CT) revealed a mass in the middle lobe of the right lung. Transbronchial lung biopsies revealed the presence of SRCA (70%) mixed with poorly-differentiated adenocarcinoma (30%). Immunohistochemically, the SRCA cells were positive for cytokeratin (CK)7 and thyroid transcription factor-1, and negative for CK20. An inversion of the EML4-ALK gene was detected by fluorescence in situ hybridization and crizotinib was injected by nasogastric tube. The patient was highly responsive to crizotinib. The symptoms of dyspnea were relieved and the volumes of pericardial and pleural effusion were gradually reduced. A CT scan revealed lung tumor regression. The overall response was a partial response. Therefore, crizotinib exists an attractive therapeutic option for patients with SRCA. However, in the present study, acquired drug resistance to crizotinib developed after only one month of treatment. It would consequently be valuable to investigate the mechanisms underlying acquired crizotinib resistance in future studies.