ABSTRACT
Lung cancer is the most common cause of cancer-related death in the world. Long non-coding RNAs (lncRNAs) are longer than 200 nucleotide transcripts, and are not translated into protein. The lncRNA linc00662 is overexpressed in lung cancer; however, its role in lung cancer is still unknown. In our study, by analyzing the TCGA data, we found that linc00662 was overexpressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). We knocked-down the expression of linc00662 using siRNA, and found that silencing linc00662 significantly inhibited the proliferation and colony formation of the lung cancer cell lines A549 and H460. We also found that knockdown of linc00662 increased the expression of the microRNA miR-145-5p and decreased the expression of the platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2) gene. We further show that linc00662 binds with miR-145-5p, and that miR-145-5p binds to the 3'UTR of PAFAH1B2. miR-145-5p negatively regulates PAFAH1B2 both at the mRNA and the protein level. Loss of miR-145-5p abolished the inhibitory effects of silencing linc00662 on the proliferation and colony formation of A549 and H460 cells. These findings indicate that linc00662 functions as an oncogene by acting as a competing endogenous RNA (ceRNA) and sponges and regulates miR-145-5p in lung cancer, and thus may provide a potential target for treating lung cancer.
Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism , Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Lung Neoplasms/pathology , MicroRNAs/genetics , Microtubule-Associated Proteins/metabolism , RNA, Long Noncoding/genetics , 1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics , Aged , Apoptosis , Biomarkers, Tumor/genetics , Cell Proliferation , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Male , Microtubule-Associated Proteins/genetics , Middle Aged , Prognosis , Survival Rate , Tumor Cells, CulturedABSTRACT
Lung cancer is the most common cause of cancer-associated mortality globally. Long non-coding RNAs (lncRNAs) are transcripts with a length of >200 nucleotides, which are not translated into proteins. Growing evidence has indicated that certain lncRNAs are associated with various biological processes in cancer. However, the functions of KCNK15 and WISP2 antisense RNA 1 (KCNK15-AS1) in lung cancer carcinogenesis and progression have remained elusive. The present study indicated that KCNK15-AS1 was overexpressed in lung adenocarcinoma tissues compared with paracancerous normal tissues, and the high expression of KCNK15-AS1 was significantly associated with poor prognosis compared with the patients with low expression (P<0.001). Furthermore, the knockdown of KCNK15-AS1 was performed in A549 and H460 lung cancer cells with small interfering RNA, resulting in a significant inhibition of the proliferation, a decrease in the mRNA and protein expression of cyclin D1 (CCND1) and epidermal growth factor receptor (EGFR), in addition to the phosphorylation of protein kinase B, with a concomitant increase in the expression of microRNA (miR)-202 and miR-370 compared with negative control group. Rescue experiments demonstrated that the inhibition of miR-202 or miR-370 partially recovered the EGFR and CCND1 expression and the proliferation rates, which were reduced by KCNK15-AS1 silencing. In conclusion, these results suggested that KCNK15-AS1 functions as an oncogene via regulating the miR-202/miR-370/EGFR axis in lung cancer and may provide a potential target for lung cancer treatment.
ABSTRACT
Cancer is the leading cause of morbidity and mortality worldwide, particularly lung cancer. Heat shock proteins and their upstream heat shock factors are involved in the occurrence of cancer and have been widely researched. However, the role of heat shock factor 2 (HSF2) in lung cancer remains unclear. In the present study, expression levels of HSF2 in lung cancer tissues from 50 lung cancer patients were detected by reverse transcription quantitative polymerase chain reaction, and 76% (38/50) were upregulated compared with the matched normal tissues. This suggested possible involvement of HSF2 in lung cancer. To additionally investigate the role of HSF2 in lung cancer occurrence, a plasmid encoding HSF2 was constructed. HSF2 was over expressed in normal lung epithelial BEAS-2B cells and lung cancer A549 cells. The results showed that HSF2 overexpression promoted cell proliferation and cell migration in BEAS-2B and A549 cells. Additional experiments showed that the HSF2-induced cell proliferation and cell migration were dependent on induction of HSPs, particularly HSP27 and HSP90, as co-transfection of HSP27 small interfering RNA (siRNA) or HSP90 siRNA attenuated HSF2-induced cell growth and migration. In conclusion, the present study showed that HSF2 is aberrantly expressed in lung cancer, and it may be an upstream regulator of HSPs, which may strongly affect cell growth and cell migration. Additional studies are required to explain the detailed mechanism between lung cancer, HSF2, HSPs and other possible signaling pathways.
ABSTRACT
In order to explore the association between cadherin 13 (CDH13) gene promoter methylation and lung carcinoma (LC) risk, we carried out a meta-analysis with searching of PubMed, Web of Science. Ultimately, 17 articles were identified and analysised by STATA 12.0 software. Overall, we found a significant relationship between CDH13 promoter methylation and LC risk (odds ratio=6.98, 95% confidence interval: 4.21-11.56, p<0.001). Subgroup analyses further revealed that LC risk was increased for individuals carrying the methylated CDH13 compared with those with unmethylated CDH13. Hence, our study identified a strong association between CDH13 gene promoter methylation and LC and highlighted a promising potential for CDH13 methylation in LC risk prediction.
