BPTF promotes glioma development through USP34-mediated de-ubiquitination of FOXC1.

Glioma is the most prevalent malignant tumor of the brain, and the study of the molecular mechanisms associated with its development has important clinical significance. Our previous study found that BPTF promotes the malignant phenotype of glioma and is significantly associated with poor prognosis; the downstream regulatory mechanisms are explored in this study. Western blot and immunohistochemical staining were used to detect protein expression in cells or tissues. BPTF knockdown as well as FOXC1-overexpressing lentiviruses were used in combination for the construction of the U251 cell model, leading to functional rescue experiments. CCK8 assay, flow cytometry, scratch assay, and Transwell assay were used to detect cell proliferation, apoptosis, and migration, respectively. Finally, immunoprecipitation assays, combined with western blot (WB), were used to detect the interaction between proteins as well as the level of ubiquitination modification. The obtained results suggested that BPTF knockdown may inhibit the malignant behavior of glioma cells by downregulating FOXC1 expression. Moreover, FOXC1 expression was significantly higher in glioma tissues than in normal brain tissues and was significantly associated with higher tumor stage and worse patient prognosis. Finally, the mechanism of FOXC1 regulation by BPTF was found to result from the affected protein stability of FOXC1 through USP34-mediated de-ubiquitylation. In conclusion, the BPTF/FOXC1 axis was identified as a key promotor in glioma development and may be a potential target in the inhibition of glioma development.

Apatinib plus Radiotherapy on the Expression of CEA and VEGF in Advanced Oligometastatic Non-Small-Cell Lung Cancer.

Objective: The purpose of this study was to evaluate the clinical efficacy of apatinib plus concurrent radiotherapy on carcinoma embryonic antigen (CEA) and vascular endothelial growth factor (VEGF) expression in patients with non-small-cell lung cancer (NSCLC) with oligometastases. Methods: This is a prospective randomized controlled trial. Sixty-four patients with oligometastatic NSCLC who were treated in the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2017 to January 2019 were randomly assigned into the control group and the study group, with 32 cases in each group. The control group was treated with stereotactic body radiotherapy (SBRT), and the study group was treated with apatinib. Results: The overall response rate (ORR) of the study group was significantly higher than that of the control group. The carcinoma embryonic antigen (CEA) and the vascular endothelial growth factor (VEGF) in the two groups were significantly decreased, with lower results in the study group compared to the control group. The 12-month and 24-month overall survival (OS) of the study group were significantly higher than those of the control group. There was no significant difference in progression-free survival (PFS) between the two groups. The median OS in the control group was 20.0 months, and the study group had not yet reached the median OS; the OS in the study group was significantly higher than that in the control group. There was no significant difference in adverse reactions between the two groups. Conclusion: For patients with oligometastatic lung cancer, apatinib combined with chemotherapy can significantly improve clinical efficacy, reduce tumor marker expression, and extend overall survival with good safety profiles.

Construction of endogenous RNA regulatory network for colorectal cancer based on bioinformatics. / åŸºäºŽç”Ÿç‰©ä¿¡æ¯å­¦æž„å»ºç»“è‚ ç™Œå† æºæ€§RNA网络.

OBJECTIVES: The high morbidity and mortality of colorectal cancer (CRC) have posed great threats to human health. Circular RNA (circRNA) and microRNA (miRNA), acting as competing endogenous RNAs (ceRNAs), have been found to play vital roles in carcinogenesis. This paper aims to construct a circRNA/miRNA/mRNA regulatory network so as to explore the molecular mechanism of CRC. METHODS: The sequencing data of circRNA from CRC were obtained from Gene Expression Omnibus (GEO). The differential circRNA was screened and its structure was identified by Cancer-specific CircRNA Database (CSCD); the sequencing data of miRNA and messenger RNA (mRNAs) were downloaded from The Cancer Genome Atlas (TCGA) database and the differentially expressed genes were screened; the corresponding miRNA of differential circRNAs were predicted by CircInteractome database; DIANA, Miranda, PicTar, and TargetScan databases were used to predict the target genes of different miRNAs; the target genes from Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were enriched by R language; String database combined with Cytoscape 3.7.2 software was used to construct protein-protein interaction (PPI) network and hub genes were screened; the expressions of mRNAs in the Top10 hub genes were verified in CRC. The network diagrams of circRNAs/miRNAs/mRNAs and circRNAs/miRNAs/Top10 hub mRNAs were constructed by Cytoscape3.7.2. Real-time PCR was used to examine the expression levels of hsa_circRNA_0065173, hsa-mir-450b, hsa-mir-582, adenylate cyclase 5 (ADCY5), muscarinic acetylcholine receptor M2 (CHRM2), cannabinoid receptor 1 (CNR1), and lysophosphatidic acid receptor 1 (LPAR1) in the CRC tissues and the adjacent normal tissues. RESULTS: A total of 14 differential circRNAs were identified, and 8 were found in CSCD; 34 miRNAs targeted by circRNAs were obtained. The PPI network was constructed, and the Top10 hub genes were identified, which were CHRM2, melanin concentrating hormone receptor 2 (MCHR2), G-protein gamma 3 subunit (GNG3), neuropeptide Y receptor Y1 (NPY1R), CNR1, LPAR1, ADCY5, adenylate cyclase 2 (ADCY2), gamma 7 (GNG7) and chemokine 12 (CXCL12), respectively. The expressions of Top 10 hub genes were also verified, and the results showed that the Top 10 hub genes were down-regulated in CRC; the constructed network diagram showed that hsa_circRNA_0065173 may regulate ADCY5, CHRM2, and Hsa-mir-450b by modulating hsa-mir-450b and hsa-mir-582. CNR1 and LPAR1 genes might serve as potentially relevant targets for the treatment of CRC. Real-time PCR results showed that the expression levels of hsa_circRNA_0065173, ADCY5, CHRM2, CNR1 and LPAR1 in the CRC tissues were significantly reduced compared with the adjacent normal tissues (all P<0.05); the expression levels of hsa-mir-450b and hsa-miR-582 were significantly increased (both P<0.05). CONCLUSIONS: In this study, a potential circRNAs/miRNAs/mRNAs network is successfully constructed, which provides a new insight for CRC development mechanism through ceRNA mediated by circRNAs.

Association of tumor downstaging after neoadjuvant chemotherapy with survival in patients with locally advanced nasopharyngeal carcinoma: a retrospective cohort study.

PURPOSE: Assessing the downstaging effects of neoadjuvant chemotherapy (NACT) in patients with locally advanced nasopharyngeal carcinoma (LANPC) and predicting response to treatment remain challenging. The present study aimed to evaluate the long-term prognosis of downstaging after NACT in patients with LANPC and to investigate the prognostic value of post-NACT tumor downstaging on treatment outcomes in the era of concurrent chemoradiotherapy (CCRT). METHODS: This retrospective study included 226 patients with stage III (n = 188) and IVA (n = 38) NPC admitted to Haikou People's Hospital between 1 October 2009 and 1 October 2012. The patients were grouped as downstaging or no after NACT. Overall survival (OS), locoregional failure-free survival (LFFS), and distant failure-free survival (DFFS) were analyzed. RESULTS: Among 226 patients, 196 (86.7%) were in the downstaging group and 30 (13.3%) were in the non-downstaging group. The longest follow-up was 76 months, and the median was 45 months. The 3-year OS rates of the downstaging group and non-downstaging group were 91.0% (95% CI 0.89-0.93) and 69.5% (95% CI 0.66-0.72) (P = 0.005). The 5-year OS rates were 81.6% (95% CI 0.78-0.86) and 53.3% (95% CI 0.49-0.61) (P = 0.001). N downstaging (3-year OS, HR 0.491, 95% CI 0.221-0.881, P = 0.022; 5-year OS, HR = 0.597, 95% CI 0.378-0.878, P = 0.021) was independently associated with OS. CONCLUSION: In the treatment of LANPC, the patients with downstaging after NACT have a better prognosis than those without downstaging. This study suggests that NACT can improve the prognosis for patients with LANPC if there is downstaging.

Bromodomain PHD­finger transcription factor promotes glioma progression and indicates poor prognosis.

Glioma is one of the most deadly central nervous system tumors around the world. Uncontrollable cell proliferation and invasion are key factors of cancer progression as well as glioma. Available evidence suggests that bromodomain PHD­finger transcription factor (BPTF) plays an important role in stem cell proliferation and differentiation, as well as in progression of some tumors, but there is little data on glioma. Therefore, the present study aimed to explore the functional role and potential clinical value of BPTF in glioma. Public database, real­time PCR and western blotting were used to detect the expression of BPTF in glioma tissue and cells. The relationship between BPTF with clinicopathological features and the prognosis of glioma patients was analyzed by immunohistochemical staining in 113 cases of paraffin­embedded primary glioma specimens. Furthermore, cytological experiments were conducted to elucidate the functional role of BPTF in glioma U251 cells, as well as the potential molecular mechanism. The expression of BPTF in glioma tissues was significantly higher than that in normal brain tissues. The association analysis results revealed that high BPTF expression was significantly associated with WHO grade and tumor size. Survival analysis revealed that the BPTF high­expression group had poorer overall survival (OS) and progression­free survival (PFS) compared with the low­expression group. Univariate and multivariate Cox regression analyses revealed that BPTF expression was an independent prognostic factor for the OS and PFS of glioma patients. Cytological experiments revealed that BPTF overexpression could significantly promote the proliferation, migration and invasion of human glioma U251 cells. A study of the underlying mechanism indicated that BPTF promoted glioma progression via MYC signaling. Our results preliminarily indicated that BPTF promoted glioma progression via MYC signaling and may be a potential prognostic biomarker and therapeutic target for glioma patients.

Three-dimensional conformal radiotherapy by delineations on CT-based simulation in different respiratory phases for the treatment of senile patients with non-small cell lung cancer.

AIM: This study aimed to evaluate the application of three-dimensional conformal radiotherapy (3D-CRT) for elderly patients with non-small cell lung cancer (NSCLC) based on computed tomography (CT) simulations in different respiratory phases. METHODS: A total of 64 patients aged >70 years old with NSCLC were treated by 3D-CRT using CT images in different respiratory phases. The gross tumor volumes (GTVs) at the end of inspiration and end of expiration were combined to obtain the total GTV, which was close to the motional range of tumors during respiration, and no additional expansion of the clinical target volume (CTAV) to planning target volume (PTV) (CTAV:PTV) was included during the recording of respiratory movements. Patients were also planned according to the classic 3D-CRT approach. Efficacy, prognostic factors, and side effects were evaluated. RESULTS: Compared with the classic approach, the average PTV was 18.9% lower (median: 17.3%), and the average lung volume receiving a prescribed dose for a tumor was 22.4% lower (median: 20.9%). The 1-, 2-, and 3-year survival rates were 70.6%, 54.9%, and 29.4%, respectively, with an overall tumor response rate of 79.7%. The Karnofsky performance status and N stage were independent prognostic factors, whereas age was not. CONCLUSION: Without affecting therapeutic effects, CT simulations in different respiratory phases were well-tolerated in elderly patients with NSCLC, could effectively reduce PTV, and could improve the quality of life.