MicroRNA-related single-nucleotide polymorphism of XPO5 is strongly correlated with the prognosis and chemotherapy response in advanced non-small-cell lung cancer patients.

This study was performed to investigate if the microRNA-related single-nucleotide polymorphisms (miR-SNPs) of XPO5 gene predicted the prognosis and pathological features of advanced non-small-cell lung cancer patients receiving chemotherapy. A total of 131 advanced non-small-cell lung cancer (NSCLC) patients were recruited. MicroRNA (miRNA) binding site prediction software was adopted for the prediction and screening of SNPs in XPO5 and miRNA binding regions. Polymerase chain reaction (PCR) amplification was further performed. Time-dependent survival-free curves were constructed using the Kaplan-Meier technique. Univariate and the multivariate survival analyses were conducted for confirmation of prognostic factor for advanced NSCLC patients receiving chemotherapy. There were no significant differences of SNP distribution frequencies between groups, without statistical significance (P > 0.05). Included clinical pathological features and chemotherapy regimens showed no apparent statistical significance in influencing the curative effect of chemotherapy in advanced NSCLC patients (all P > 0.05). While the objective response rate (ORR) in patients who carried AA and AC genotype was 35.48 and 51.22 %, respectively, with statistically significant difference (P < 0.05). Univariate survival analysis indicated that patients who carried AA genotype showed a significantly lower 5-year survival rate to those who carried AC genotype (P < 0.05). And, considering pathological features, statistical significance was found in patients with different pathological types, lymph node metastasis, differentiation degree, T staging, and pathological staging (all P < 0.05). Multivariate analysis results indicated that the SNP sites of rs11077 might be an independent prognostic factor of advanced NSCLC patients receiving chemotherapy (risk ratio [RR] = 0.346; 95 % confidence interval [95 % CI] = 0.174-0.685, P = 0.002). Other clinical features were all considered to have no apparent effect in influencing the prognostic outcomes of advanced NSCLC patients receiving chemotherapy except lymph node metastasis (P < 0.05). miR-SNP rs11077 of XPO5 may be independently connected with the prognosis and chemotherapy response of advanced NSCLC patients, and patients with AC genotype have relatively improved prognostic outcomes and better curative effect of chemotherapy than those with AA allele of XPO5. Further, lymph node metastasis may be also involved in influencing the prognosis of advanced NSCLC patients.

Matrix metalloproteinase activity in early-stage lung cancer.

BACKGROUND: The matrix metalloproteinases (MMPs)-2, -9 and -7 are thought to be associated with tumor invasion, metastasis, and angiogenesis. However, their possible roles in early-stage lung cancer are not clear. We measured the activity of MMP-2, -7 and -9 in early-stage lung cancer tissues. MATERIAL AND METHODS: Normal lung tissues and cancer tissues were collected from 60 consecutive stage-I non-small cell lung cancer (NSCLC) patients. The activities of MMP-2 and MMP-9 were determined by gelatin zymography, and the activity of MMP-7 was determined by casein zymography. Furthermore, the ratio of the active form of MMP-2 in tumor tissue (T) compared with normal tissue (N) was determined, and the survival in the groups with different MMP-2 T:N ratio was compared. RESULTS: The activity of both MMP-2 and MMP-9 was detected in all cancer and normal tissues. Interestingly, MMP-9 activity was significantly reduced, whereas MMP-2 activity was significantly increased, in cancer tissues compared to normal tissues. The survival rate of the MMP-2 T:N ratio > 2.5 group was 57.45%, which was significantly reduced compared with that of the T:N ratio ≤ 2.5 group (86.78%). CONCLUSION: Our findings suggest that MMP-2, but not MMP-9 and MMP-7, may be implicated in early-stage tumor invasion, metastasis, and angiogenesis in NSCLC.

TBX18 knockdown sensitizes esophageal squamous cell carcinoma to radiotherapy by blocking the CHN1/RhoA axis.

OBJECTIVE: Radioresistance is a challenge in the effective treatment of esophageal squamous cell carcinoma (ESCC). Herein, this research ascertained whether TBX18 reduced the radiosensitivity of ESCC. METHODS: Bioinformatics analysis was utilized to retrieve differentially expressed genes. Then, the expression of corresponding candidate genes was tested using qRT-PCR in ESCC clinical specimens, and TBX18 was selected for subsequent experiments. The binding between TBX18 and CHN1 was evaluated by dual-luciferase reporter and ChIP assays, and the relationship between CHN1 and RhoA was identified by GST pull-down. Ectopic expression or knockdown experiments and radiation treatment were performed in cells and the nude mouse xenograft model to clarify the impacts of TBX18, CHN1, and RhoA on radiosensitivity in ESCC. RESULTS: Bioinformatics analysis and qRT-PCR retrieved upregulated TBX18 in ESCC for the follow-up study. Additionally, TBX18 was positively correlated with CHN1 in ESCC clinical specimens. Mechanistically, TBX18 bound to the CHN1 promoter region to transcriptionally activate CHN1, thus elevating RhoA activity. Moreover, TBX18 knockdown reduced ESCC cell proliferation and migration while augmenting their apoptosis after radiation, which was negated by further overexpressing CHN1 or RhoA. CHN1 or RhoA knockdown diminished ESCC cell proliferation and migration, as well as enhanced cell apoptosis, subsequent to radiation. Likewise, TBX18 overexpression increased ESCC cell autophagy after radiation, which was partially reversed by knockdown of RhoA. The results of in vivo xenograft experiments in nude mice were concurrent with the in vitro results. CONCLUSION: TBX18 knockdown lowered CHN1 transcription and thus reduced RhoA activity, which sensitized ESCC cells to radiotherapy.

circCCND1 Regulates Oxidative Stress and FGF9 to Enhance Chemoresistance of Non-Small Cell Lung Cancer via Sponging miR-187-3p.

Circular RNAs have been shown to regulate cancer tumorigenesis and drug resistance. Recently, circCCND1 is reported to promote laryngeal squamous cell carcinoma; however, whether circCCND1 is implicated in non-small cell lung cancer (NSCLC) remains unclear. In this research, The Cancer Genome Atlas data of lung adenocarcinoma were analyzed to show gene expression and overall survival. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide assay and cell colony formation assay were utilized to measure cell viability and proliferation of A549 and HCC827. Apoptosis was detected by TdT-mediated dUTP Nick-End Labeling assay. Besides, reverse transcription-quantitative PCR was used to examine gene expression. We observed that circCCND1 was significantly upregulated in lung cancer cells and patients. circCCND1 knockdown attenuated cell proliferation and induced apoptosis under cisplatin treatment. Mechanistically, circCCND1 interacted with miR-187-3p to regulate reactive oxygen species and FGF9 in NSCLC cells. Finally, miR-187-3p was demonstrated to rescue circCCND1 knockdown-modulated chemoresistance of NSCLC cells. In this study, our conclusions facilitate the understanding of NSCLC drug resistance to cisplatin.