Mechanism of PWAR6 regulating cisplatin drug sensitivity in non-small cell lung cancer through miR-577/PHACTR1.

lncRNA Prader Willi/Angelman Region RNA 6 (PWAR6) is considered to play a protective lncRNA in glioma, but, the role of PWAR6 in the occurrence and cisplatin resistance of non-small cell lung cancer (NSCLC) is elusive. In the study, we aimed to assess the role of PWAR6 in the cisplatin resistance of NSCLC. Based on the oebiotech and TargetScanHuman database, we predicted the interaction between PWAR6, miR-577 and PHACTR1. We then used small interfering RNA (siRNA), miRNA mimics and dual-luciferase reporter assay to explore the regulatory role of PWAR6/miR-577PHACTR1. Based on the online database, miR-577 can interact with PWAR6 and PHACTR1. Soon afterwards, we observed that the expression of PWAR6 and PHACTR1 was increased, while miR-577 expression was decreased in A549/DDP cells. And the cell viability was decreased, while cell apoptosis was increased in A549/DDP cells. What's more, PWAR6 knockdown can promote the expression of miR-577 and inhibit the expression of PHACTR1. PWAR6 knockdown elevated cell proliferation and reduced cell apoptosis of A549/DDP cells. Interestingly, we found that miR-577 can interact with PHACTR1 to regulate the proliferation and apoptosis of A549/DDP cells. To conclude, we speculated that PWAR6 knockdown elevated cell proliferation and reduced cell apoptosis of A549/DDP cells via miR-577/PHACTR1, providing the theoretical basis for the clinical treatment of NSCLC patients.

The Biological Role of Lncrna SNHG6 in Non-Small Cell Lung Cancer Cells Via Targeting P21.

Objective: To investigate the influence of long non-coding ribonucleic acid (lncRNA) small nucleolar RNA host gene 6 (SNHG6) on proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells and to provide a theoretical basis for the clinical treatment of NSCLC. Methods: This study included 25 samples of NSCLC and 20 normal tissues as the experimental group. Fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect lncRNA SNHG6 and p21. The relationship between lncRNA SNHG6 and p21 in NSCLC tissues was analyzed statistically. Colony formation assay and flow cytometry were used to determine the cell cycle distribution and cell apoptosis. Methyl thiazolyl tetrazolium (MTT) assay was used to determine cell proliferation, and Western blotting (WB) was used to measure the protein expression of p21. Results: The expression level of SNHG6 [(1.98 ± 0.23) vs. (4.46 ± 0.52)] (P < .01) was significantly higher, but p21 expression [(1.02 ± 0.23) vs. (0.33 ± 0.15)] (P < .01) was lower in the 25 cases of NSCLC tissues than in the control group. The expression of SNHG6 was negatively correlated with p21 (r2 = 0.2173, P = .0188). Transfection of SNHG6 small interfering RNA (siRNA) (si-SNHG6) in HCC827 and H1975 cells significantly reduced the level of SNHG6. The viability of BEAS-2B cells transfected with pcDNA-SNHG6 had a more robust proliferative and colony-forming capacity than normal cells (P < .01). Up-regulation of SNHG6 promoted the formation of the malignant phenotype and proliferative capacity of BEAS-2B cells. Proliferation, colony-forming capacity, and G1 phase of the cell cycle in HCC827 and H1975 cells were significantly repressed via influencing the apoptosis and p21 expression after the knockdown of SNHG6 (P < .01). Conclusion: Silencing lncRNA SNHG6 represses the proliferation and facilitates the apoptosis of NSCLC cells through regulating p21.

Association of the polymorphisms in TP63 rs6790167 with risk for lung cancer in Hain-an Han population / 中国肿瘤临床

Objective:To evaluate the association between the polymorphisms in TP63 rs6790167 and lung cancer. Methods:We per-formed a case-control study with 258 patients and 270 controls. Genomic DNA was extracted using a blood genome extraction kit. Ge-notyping was conducted using allele-specific polymerase chain reaction (AS-PCR). Results:No significant difference was observed in the genotype of TP63 rs6790167 between cases and controls, and allele frequencies significantly elevated in the cases (P=0.045). In a further stratified analysis by gender and smoking status, the frequencies of the GG genotype and G allele of rs6790167 were signifi-cantly higher in non-smoking male patients with lung adenocarcinoma (P=0.000, P=0.001), individuals with GG genotype had a higher risk for lung adenocarcinoma in non-smoking man (OR=6.66, 95%CI:2.16-20.41). Individuals with G allele had a higher risk for lung ad-enocarcinoma in a non-smoking man (OR=2.54, 95%CI:1.42-4.56) in comparison with individuals with A allele. Conclusion:We found that the polymorphisms of TP63 rs6790167 were associated with the risk for lung adenocarcinoma in non-smoking men and that these polymorphisms may be a predictor for lung adenocarcinoma in non-smoking men.

Association of Single Nucleotide Polymorphisms in the Apoptosis-Related Genes TP63 and CD40 with Risk for Lung Cancer in a Chinese Han Population.

Apoptosis plays a critical role in tumorigenesis. TP63 inhibits the pro-apoptosis function of TP53, and CD40 increases expression of anti-apoptotic proteins. Two single nucleotide polymorphisms (SNPs), rs6790167 (g243059A>G) in intron 9 of TP63 and rs1535045 (g6194C>T) in intron 1 of CD40 respectively, may affect the susceptibility of lung cancer. To evaluate the association of these SNPs with lung cancer, we performed a case-control study with 258 patients, including 149 adenocarcinoma and 47 small cell lung cancer, and 270 controls. Genotyping was conducted using allele-specific polymerase chain reaction and pyrosequencing. We found that rs6790167 and rs1535045 are associated with the risk of lung adenocarcinoma (P = 0.048) and small cell lung cancer (P = 0.019), respectively. Non-smoking males carrying the GG genotype of rs6790167 had higher risk for lung adenocarcinoma than individuals carrying the AA genotype (OR = 7.58, 95% CI: 2.43-23.65). Compared to the TT genotype of rs1535045, non-smoking women with the CC genotype had higher risk for lung adenocarcinoma (OR = 4.20, 95% CI: 1.34-13.12). After stratified analysis based on clinical characteristics, the frequency of the CC genotype of rs1535045 was higher in patients at I-II stages (P = 0.013) or patients whose tumor markers were negative (P = 0.003). Individuals carrying both the GG genotype of rs6790167 and the CC genotype of rs1535045 were associated with significantly higher risk for lung adenocarcinoma. Thus, the polymorphisms in the TP63 and CD40 genes are associated with lung cancer in a Chinese Han population.