A non-linear partial least squares based on monotonic inner relation.

A novel regression model, monotonic inner relation-based non-linear partial least squares (MIR-PLS), is proposed to address complex issues like limited observations, multicollinearity, and nonlinearity in Chinese Medicine (CM) dose-effect relationship experimental data. MIR-PLS uses a piecewise mapping function based on monotonic cubic splines to model the non-linear inner relations between input and output score vectors. Additionally, a new weight updating strategy (WUS) is developed by leveraging the properties of monotonic functions. The proposed MIR-PLS method was compared with five well-known PLS variants: standard PLS, quadratic PLS (QPLS), error-based QPLS (EB-QPLS), neural network PLS (NNPLS), and spline PLS (SPL-PLS), using CM dose-effect relationship datasets and near-infrared (NIR) spectroscopy datasets. Experimental results demonstrate that MIR-PLS exhibits general applicability, achieving excellent predictive performances in the presence or absence of significant non-linear relationships. Furthermore, the model is not limited to CM dose-effect relationship research and can be applied to other regression tasks.

New research for detecting complex associations between variables with randomness.

Many correlation analysis methods can capture a wide range of functional types of variables. However, the influence of uncertainty and distribution status in data is not considered, which leads to the neglect of the regularity information between variables, so that the correlation of variables that contain functional relationship but subject to specific distributions cannot be well identified. Therefore, a novel correlation analysis framework for detecting associations between variables with randomness (RVCR-CA) is proposed. The new method calculates the normalized RMSE to evaluate the degree of functional relationship between variables, calculates entropy difference to measure the degree of uncertainty in variables and constructs the copula function to evaluate the degree of dependence on random variables with distributions. Then, the weighted sum method is performed to the above three indicators to obtain the final correlation coefficient R. In the study, which considers the degree of functional relationship between variables, the uncertainty in variables and the degree of dependence on the variables containing distributions, cannot only measure the correlation of functional relationship variables with specific distributions, but also can better evaluate the correlation of variables without clear functional relationships. In experiments on the data with functional relationship between variables that contain specific distributions, UCI data and synthetic data, the results show that the proposed method has more comprehensive evaluation ability and better evaluation effect than the traditional method of correlation analysis.

An improved particle swarm optimization combined with double-chaos search.

Particle swarm optimization (PSO) has been successfully applied to various complex optimization problems due to its simplicity and efficiency. However, the update strategy of the standard PSO algorithm is to learn from the global best particle, making it difficult to maintain diversity in the population and prone to premature convergence due to being trapped in local optima. Chaos search mechanism is an optimization technique based on chaotic dynamics, which utilizes the randomness and nonlinearity of a chaotic system for global search and can escape from local optima. To overcome the limitations of PSO, an improved particle swarm optimization combined with double-chaos search (DCS-PSO) is proposed in this paper. In DCS-PSO, we first introduce double-chaos search mechanism to narrow the search space, which enables PSO to focus on the neighborhood of the optimal solution and reduces the probability that the swarm gets trapped into a local optimum. Second, to enhance the population diversity, the logistic map is employed to perform a global search in the narrowed search space and the best solution found by both the logistic and population search guides the population to converge. Experimental results show that DCS-PSO can effectively narrow the search space and has better convergence accuracy and speed in most cases.

Feature selection based on neighborhood rough sets and Gini index.

Neighborhood rough set is considered an essential approach for dealing with incomplete data and inexact knowledge representation, and it has been widely applied in feature selection. The Gini index is an indicator used to evaluate the impurity of a dataset and is also commonly employed to measure the importance of features in feature selection. This article proposes a novel feature selection methodology based on these two concepts. In this methodology, we present the neighborhood Gini index and the neighborhood class Gini index and then extensively discuss their properties and relationships with attributes. Subsequently, two forward greedy feature selection algorithms are developed using these two metrics as a foundation. Finally, to comprehensively evaluate the performance of the algorithm proposed in this article, comparative experiments were conducted on 16 UCI datasets from various domains, including industry, food, medicine, and pharmacology, against four classical neighborhood rough set-based feature selection algorithms. The experimental results indicate that the proposed algorithm improves the average classification accuracy on the 16 datasets by over 6%, with improvements exceeding 10% in five. Furthermore, statistical tests reveal no significant differences between the proposed algorithm and the four classical neighborhood rough set-based feature selection algorithms. However, the proposed algorithm demonstrates high stability, eliminating most redundant or irrelevant features effectively while enhancing classification accuracy. In summary, the algorithm proposed in this article outperforms classical neighborhood rough set-based feature selection algorithms.

Retraction Note: Mir-655 up-regulation suppresses cell invasion by targeting pituitary tumor-transforming gene-1 in esophageal squamous cell carcinoma.

The Editor-in-Chief has retracted this article [1] because Figure 3a overlaps with Figure 2 in [2]. An investigation by Zhengzhou University has confirmed this. The data reported in this article are therefore unreliable. There is also considerable text overlap with a previously published article [3]. Guoqiang Zhao does not agree with this retraction. The other authors have not responded to correspondence from the editor about this retraction.

Retraction Note: miR-663 attenuates tumor growth and invasiveness by targeting eEF1A2 in pancreatic cancer.

The Editor-in-Chief has retracted this article [1] because Figure 6b overlaps with Figure 8 of [2] and Figure 4a overlaps with Figure 2b of [3].

Inhibitory effect of α-solanine on esophageal carcinoma in vitro.

α-solanine, a bioactive component and one of the major steroidal glycoalkaloids in potatoes, has been observed to inhibit growth and induce apoptosis in cancer cells. However, the antitumor efficacy of α-solanine on esophageal carcinoma has yet to be fully elucidated. In the present study, the antitumor efficacy of α-solanine against human esophageal carcinoma cells was investigated. It was determined that α-solanine inhibited the growth and proliferation of human esophageal EC9706 and Eca109 cancer cells in a dose-dependent manner, as well as the cell migration and invasion. In addition, the apoptotic rate was increased in the cancer cells treated with α-solanine in a dose-dependent manner, compared with that of the control group (P<0.05). The expression levels of tumor metastasis-related proteins, including matrix metalloproteinase (MMP)-2 and MMP-9, were reduced in the cells treated with α-solanine, as compared with the control group. Conversely, significantly higher expression levels of E-cadherin were detected in the α-solanine-treated groups, as compared with the control group (P<0.05). Therefore, the current results provide a novel insight into the anti-tumor mechanism of α-solanine, and suggest that α-solanine is a potential agent for the prevention and treatment of esophageal carcinoma.

miR-15a induces cell apoptosis by targeting BCL2L2 and BCL2 in HPV-positive hypopharyngeal squamous cell carcinoma.

Aberrant expression of miR-15a was recently reported in several types of cancers; however, its role in HPV-positive hypopharyngeal squamous cell carcinoma (HSCC) remains obscure. In the present study, we investigated the mechanism by which miR-15a induces HPV-positive HSCC apoptosis. Synthetic miR-15a mimics were transfected into FaDu cells (HPV-negative), and the miR-15a inhibitor was transfected into HPV-positive HSCC cells. miR-15a expression was analyzed by RT-PCR, and BCL2L2 and BCL2 were analyzed by western blotting. The Hochest 33342/propidium iodide (PI) and caspase-3/-9 assays, and Annexin V staining were used to assess the effect of miR-15a on apoptosis. After transfection, overexpression of miR-15a in the FaDu cells was associated with significantly decreased BCL2L2 and BCL2 expression and a significant increase in the apoptosis rate. The opposite results were observed in HPV-positive HSCC, where downregulation of miR-15a suppressed apoptosis. These findings indicate that miR-15a acts as a tumor suppressor in HPV-positive HSCC.

Curcumin inhibits cell growth and induces cell apoptosis through upregulation of miR-33b in gastric cancer.

In this work, the in vitro experiments about biological mechanisms of curcumin were conducted using the gastric cancer cell lines SGC-7901 and BGC-823. After 24-h exposure to curcumin at the concentrations of 5, 10, 15, 20, and 40 µmol/L, two cells showed the decreased proliferation and increased apoptosis abilities. Real-time PCR, Cell Counting Kit-8 (CCK-8) assay, western blotting, and cell apoptosis assay were used to further study the underlying mechanisms of curcumin. The first stage of our studies showed that curcumin affected the expression of miR-33b, which, in turn, affected the expression of the X-linked inhibitor of apoptosis protein (XIAP) messenger RNA (mRNA). Next, curcumin was also identified to regulate the proliferation and apoptosis of SGC-7901 and BGC-823 cells. Further bioinformatics analysis and luciferase reporter assays proved that XIAP was one of the target genes of miR-33b. In the next stage, SGC-7901 and BGC-823 cells were treated with 20 µL curcumin, miR-33b mimics, and small interfering RNA (siRNA) of XIAP, respectively. The results showed that curcumin had similar effects on cell growth and apoptosis as the upregulation of miR-33b and the upregulation of the siRNA of XIAP. The results that followed from the restore experiments showed that curcumin affected cell growth and apoptosis presumably by upregulating the XIAP targeting in gastric cancer. Collectively, our results indicate that curcumin-miR-33b-XIAP coupling might be an important mechanism by which curcumin induces the apoptosis of SGC-7901 and BGC-823 cells.

Silencing of AP-4 inhibits proliferation, induces cell cycle arrest and promotes apoptosis in human lung cancer cells.

Activating enhancer-binding protein (AP)-4 is a member of the basic helix-loop-helix transcription factors, and is involved in tumor biology. However, the role of AP-4 in human lung cancer remains to be fully elucidated. In the present study, the expression of AP-4 in human lung cancer tissues and cells was investigated by reverse transcription-quantitative polymerase chain reaction, and it was observed that the level of AP-4 was increased in tumor tissues and cells compared with their normal counterparts. AP-4 expression was knocked down by transfection with a specific small interfering RNA (siRNA) in lung cancer cells, and this indicated that siRNA-mediated silencing of AP-4 inhibited cell proliferation, arrested the cell cycle at the G0/G1 phase and induced apoptosis by modulating the expression of p21 and cyclin D1. The results of the present study suggest that AP-4 may be an oncoprotein that has a significant role in lung cancer, and that siRNA-mediated silencing of AP-4 may have therapeutic potential as a strategy for the treatment of lung cancer.

Knockdown of long non-coding RNA TP73-AS1 inhibits cell proliferation and induces apoptosis in esophageal squamous cell carcinoma.

Recent studies have shown that long non-coding RNAs (lncRNAs) are involved in a variety of biological processes and diseases in humans, including cancer. Our study serves as the first comprehensive analysis of lncRNA TP73-AS1 in esophageal cancer. We utilized a lncRNA microarray to analyze the expression profile of lncRNAs in esophageal squamous cell carcinoma. Our results show that lncRNA TP73-AS1 and BDH2 levels are generally upregulated in esophageal cancer tissues and are strongly correlated with tumor location or TNM stage in clinical samples. LncRNA TP73-AS1 knockdown inhibited BDH2 expression in EC9706 and KYSE30 cells, whereas BDH2 knockdown repressed esophageal cancer cell proliferation and induced apoptosis via the caspase-3 dependent apoptotic pathway. Overexpression of BDH2 in lncRNA TP73-AS1 knockdown cells partially rescued cell proliferation rates and suppressed apoptosis. In mouse xenografts, tumor size was reduced in lncRNA TP73-ASI siRNA-transfected tumors, suggesting that downregulation of lncRNA TP73-AS1 attenuated EC proliferation in vitro and in vivo. In addition, BDH2 or lncRNA TP73-AS1 knockdown enhanced the chemosensitivity of esophageal cancer cells to 5-FU and cisplatin. Our results suggest that lncRNA TP73-AS1 may be a novel prognostic biomarker that could serve as a potential therapeutic target for the treatment of esophageal cancer.

miR-198 targets SHMT1 to inhibit cell proliferation and enhance cell apoptosis in lung adenocarcinoma.

MiR-198 is involved in tumorigenesis, migration, invasion, and metastasis of various malignant cancers. However, the exact expression levels of miR-198 and the molecular mechanism underlying its role in lung adenocarcinoma require further exploration. In this study, quantitative real-time PCR was applied to study miR-198 and serine hydroxymethyltransferase 1 (SHMT1) expression in 47 paired lung adenocarcinoma tissues and adjacent nontumor lung tissues. Clinicopathological characters were analyzed. Pearson's correlation analysis was used to detect the relationship between miR-198 and SHMT1 expression. The function of miR-198 was explored by measuring cell proliferation, cell apoptosis, and the cell-cycle in vitro and in vivo. The target gene of miR-198 was certified using dual luciferase report assay. We found that in lung adenocarcinoma, miR-198 was significantly downregulated and SHMT1 was inversely upregulated. A strong negative correlation was noticed between miR-198 and SHMT1 expression. Further analysis revealed that miR-198 expression was associated with TNM stage and lymph node metastasis. Upregulated miR-198 could inhibit cell proliferation, enhance cell apoptosis, and lead to cell-cycle arrest in lung adenocarcinoma, which showed a more effective alteration than SHMT1 siRNA. Moreover, we identified SHMT1 as a target gene of miR-198. In conclusion, miR-198 suppressed proliferation of lung adenocarcinoma cells both in vitro and in vivo by directly targeting SHMT1. miR-198 may be a potential therapeutic target for lung adenocarcinoma in the near future.

Effects of HPV-16 infection on hypopharyngeal squamous cell carcinoma and FaDu cells.

Hypopharyngeal squamous cell carcinoma is a common type of malignant tumor among head and neck squamous cell carcinomas (HNSCCs). Heavy smoking and/or drinking is associated with the development of HNSCC. However, HNSCC also occurs in individuals that do not drink or smoke, possibly due to infection with the human papilloma virus (HPV). HPV-16 has been shown to be closely associated with the occurrence of several types of cancers. However, its role in hypopharyngeal squamous cell carcinoma remains unclear. In the present study, we investigated the effects of HPV-16 on hypopharyngeal squamous cell carcinoma and FaDu cells. Lentiviral vectors were used to establish FaDu cells that expressed the E6 and E7 proteins of HPV-16. We used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays and western blotting to detect and determine the levels of expression for E6-E7 mRNAs and proteins. Cell Counting Kit-8 (CCK-8) assays, enzyme-linked immunosorbent assays (ELISA), Transwell assays, and flow cytometry were used to assess the effects of HPV-16 E6-E7 on the proliferation, invasion, metastasis and apoptosis of FaDu cells. Expression of microRNAs was analyzed by qRT-PCR. We found that the expression levels of HPV-16 E6-E7 were increased in FaDu cells transfected with the lentiviral vector compared with that observed in the control cells. In addition, the rates of apoptosis were decreased in the transfected cells, while proliferation was increased. The average numbers of cells penetrating the Matrigel were significantly higher than those for the controls. We detected miR-363 and miR-15a, and their expression levels were significantly increased in the HPV-16-positive patients and in FaDu cells expressing HPV-16 E6-E7. We found that HPV-16 E6-E7 appeared to inhibit apoptosis, and to increase cell proliferation, invasion and metastasis. Furthermore, miR-363 and miR-15a were overexpressed in the hypopharyngeal squamous cell carcinoma samples infected with HPV-16, and in FaDu cells stably expressing HPV-16 E6-E7. These findings may provide a new clue of the mechanisms involved in the pathogenesis of HPV-16-positive hypopharyngeal squamous cell carcinoma.

G648C variant of DNA polymerase ß sensitizes esophageal cancer to chemotherapy.

Human DNA polymerase ß (polß) is a small monomeric protein that is essential for short-patch base excision repair. It plays an important role in regulating the sensitivity of tumor cells to chemotherapy. We have previously identified a G to C point mutation at nucleotide 648 (G648C) of polß in esophageal cancer (EC). In this study, we evaluated the mutation of polß in a larger cohort of EC patients by RT-PCR and sequencing analysis. The function of the mutation was evaluated by MTT, in vivo tumor growth, and flow cytometry assays. The G648C mutation occurred in 15 (3.45 %) of 435 EC patients. In addition, patients with this mutation had significantly longer survival time than those without, following postoperative chemotherapy. Cell lines with G648C mutation in polß gene were more sensitive to treatment with 5-fluorouracil and cisplatin than those with wild-type polß. These results suggest that polß gene with G648C mutation in surgically resected esophagus may be clinically useful for predicting responsiveness to chemotherapy in patients with EC. The polß gene alteration may serve as a prognostic biomarker for EC.

The K167I variant of DNA polymerase ß that is found in Esophageal Carcinoma patients impairs polymerase activity and BER.

DNA polymerase ß (pol ß) is a key enzyme in DNA base excision repair, and an important factor for maintaining genomic integrity and stability. Esophageal carcinoma (EC) patients who have been identified as carrying the K167I variant of pol ß have been shown to have decreased life expectancy. However, it is unknown if the variant affects pol ß's functions and/or how it contributes to the initiation and progression of cancer. In this study, we expressed and purified the K167I variant. Moreover, we found that K167I significantly reduced polymerase activity. As a result, the K167I substitution reduced base excision repair (BER) efficiency when assayed in a reconstitution assay or when using cellular extracts. Finally, we observed EC cells expressing the K167I variant to be sensitive to DNA damaging agents. These results suggest the K167I variant affected pol ß biochemical activity resulting in impaired BER function, which might subsequently contribute to genomic instability and cancer development.

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma.

MicroRNAs (miRNAs) are well known as important regulators in various cancer development. In the present study, we focused on the expression and biological function of miR-1291 in esophageal squamous cell carcinoma (ESCC). Compared with adjacent non-tumorous tissue samples, qRT-PCR data showed significant downregulation of miR-1291 in 54 ESCC tissue samples (P<0.05), which was also significantly associated with lymph node metastases and clinical stage (P<0.05). Cell Counting Kit-8 (CCK-8), colony formation, Transwell and flow cytometric apoptosis assays were performed to detect the effect of miR-1291 upregulation, and the results showed inhibition of the proliferation, invasion and promotion of apoptosis in EC9706 and EC-1 cells. Using bioinformatic analyses, we found that mucin 1 (MUC1) was a potential target for miR-1291. Luciferase assays were performed to reveal that miR-1291 inhibited MUC1 expression by targeting the seed region of MUC1 3'-untranslated region (3'UTR). We also found that the expression of MUC1 lacking in 3'UTR abrogated the anti-invasion and pro-apoptosis function of miR-1291. Our results demonstrated the importance of miR-1291 in targeting MUC1 for the regulation of esophagus cancer growth, invasion and apoptosis, and may be helpful for developing new targets for early diagnosis or new therapeutic targets for ESCC.

microRNA-30b inhibits cell invasion and migration through targeting collagen triple helix repeat containing 1 in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the largest histological subgroup of lung cancer and has increased in prevalence in China over the past 5 years. The 5-year survival rate has remained at 15-20 %, with a median survival of 8-12 months. The tumorigenesis and progression of NSCLC is orchestrated by numerous oncogene and anti-oncogene mutations and insights into microRNA function have increased our understanding of the process. Here, we investigated the effects of miR-30b on NSCLC cell invasion and migration and explored the underlying molecular mechanisms involved. METHODS: Quantitative reverse transcription PCR, wound healing assay, trans-well assays, western blotting and dual luciferase assays were performed to investigate the molecular mechanisms of miR-30b in NSCLC cells. RESULTS: MiR-30b was down-regulated and Cthrc1 up-regulated in NSCLC tissues. Both were associated with tumor differentiation, TNM stage and lymph node metastases. Up-regulation of miR-30b restricted A549 and Calu-3 cell invasion and migration. Additionally, the expression of Cthrc1, matrix metalloproteinase-9 and matrix metalloproteinase-2 was reduced, while metallopeptidase inhibitor-1 expression increased. Bioinformatics analysis identified Cthrc1 as a target of miR-30b and western blotting and luciferase reporter assays confirmed that miR-30b regulates Cthrc1 by directly binding to its 3'UTR. Transfection of Cthrc1 without the 3'UTR restored the miR-30b inhibiting cell invasion. Up-regulation of miR-30b or down-regulation of Cthrc1 had potential significance in the invasion and metastasis of NSCLC. CONCLUSIONS: MiR-30b was down-regulated and Cthrc1 up-regulated in NSCLC tissues. Both of them were related to tumor differentiation, TNM stage and lymph node metastases. MiR-30b affected NSCLC cells invasion and migration by regulating Cthrc1.

MiR-499 Enhances the Cisplatin Sensitivity of Esophageal Carcinoma Cell Lines by Targeting DNA Polymerase ß.

BACKGROUND: Human DNA polymerase ß (DNA polymerase ß, polß) is a small monomeric protein essential for short-patch base excision repair (BER). It plays an important role in regulating the sensitivity of tumor cells to chemotherapy. METHODS: Luciferase reporter and western blot assays were used to determine whether polß is a major target of miR-499. CCK-8, colony-forming survival and in vivo tumor growth assays were conducted to evaluate if miR- 499 can potentially enhance the cisplatin sensitivity and therefore inhibit the proliferation of esophageal cancer (EC) cells. Flow cytometry and immunofluorescence microscopy assays were performed to evaluate whether miR-499 enhance the cisplatin sensitivity and the corresponding apoptosis in EC cells. RESULTS: polß was pinpointed as a target gene of miR- 499. Additionally, we identified that miR-499 can enhance cisplatin's function of inhibiting proliferation and of promoting apoptosis in EC9706 and KYSE30 cell lines. CONCLUSIONS: We first investigated whether miR-499 modulates polß, and observed the influence of miR-499 up-regulation on the sensitivity of EC cell lines to cisplatin treatment. Our study paves the way for more insightful understanding and application of chemotherapy in esophageal cancer in the future.

Study on expression of lncRNA RGMB-AS1 and repulsive guidance molecule b in non-small cell lung cancer.

BACKGROUND: The relationships between lncRNAs and tumors have currently become one of the focuses on cancer studies. However, there are a few studies about lncRNAs in non-small cell lung cancer (NSCLC) at present. METHODS: Microarray analysis was designed to study the expression patterns of lncRNAs in three pairs of NSCLC tissues. The expression of lncRNA RGMB-AS1 and repulsive guidance molecule b (RGMB) were detected in 72 paired NSCLC tissues and adjacent normal tissues by qRT-PCR assay. The relations of lncRNA RGMB-AS1 and RGMB expression with clinicopathological factors of NSCLC patients were explored. A549 and SPC-A-1 cells were transfected with siRNA of lncRNA RGMB-AS1 and negative control. RGMB expression level was detected by qRT-PCR assay and western blot analysis. RESULTS: The results of microarray found that 571 lncRNAs were differentially expressed in NSCLC tissues (Fold change cut-off: 5.0, P < 0.05), including 304 upregulated and 267 downregulated lncRNAs. The results of qRT-PCR showed that lncRNA RGMB-AS1 expression was significantly higher in NSCLC tissues than in adjacent normal tissues (P < 0.05), while RGMB mRNA showed an opposite trend (P < 0.05). Correlation analysis indicated that the expression of lncRNA RGMB-AS1and RGMB mRNA were inversely correlated (R(2) = 0.590, P < 0.05). While lncRNA RGMB-AS1 and RGMB expression levels in NSCLC tissues were associated with the occurrence of differentiation status, lymph node metastases and TNM stage (P < 0.05). Transfection with siRNA of lncRNA RGMB-AS1, subsequent results showed that RGMB mRNA and protein expression were upregulated (P < 0.05) in A549 and SPC-A-1 cells compared to the control groups. CONCLUSION: We identified lncRNA RGMB-AS1 was upregulated and RGMB was downregulated in NSCLC patients. Both were related to differentiation status, lymph node metastases and TNM stage. Studies also indicated that lncRNA RGMB-AS1and RGMB were inversely correlated. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7911587521528276.

Expression of long non-coding RNA DLX6-AS1 in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LAC), the primary histological type of non-small cell lung cancer (NSCLC), has displayed an increasing incidence and mortality worldwide. However, therapeutic approaches were limited. Dysregulation of some lncRNAs has been shown in various types of cancers including LAC. The aim of the present study was to vertify lncRNA DLX6-AS1 expression in LAC. METHODS: Microarray assay revealed expression profile of lncRNAs in LAC. qRT-PCR ( quantitative reverse transcription PCR) was performed to identify lncRNA DLX6-AS1 expression level in 72 paired LAC and adjacent normal lung tissues. qRT-PCR and Western blotting were used to verify that down-regulation lncRNA DLX6-AS1 decreased DLX6 (distal-less homeobox 6) mRNA and protein expression. RESULTS: Microarray analysis identified up-regulation of 272 lncRNAs and down-regulation of 635 lncRNAs in LAC tissues. The expression level of lncRNA DLX6-AS1 in LAC tissues was significantly higher compared to paired adjacent normal lung tissues (P< 0.05). In addition, its expression level was closed correlated with both histological differentiation (P = 0.004) and TNM stage (P = 0.033). qRT-PCR and Western blotting analysis showed that DLX6 mRNA and protein levels were lower in si-LncRNA group than in the NC (negative control) and Blank groups. CONCLUSIONS: Microarray analysis identified that lncRNA DLX6-AS1 was up-regulated in LAC tissues. High DLX6-AS1 expression levels were significantly associated with both histological differentiation and TNM stage. Down-regulation of lncRNA DLX6-AS1 expression decreased the DLX6 mRNA and protein levels.