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Abstract: Down-regulation of let-7 microRNA (miRNA) is a key event in lung cancer. Despite recent advances in survival signaling, the roles of let-7 in the context of lung cancer are not fully clear. In this study, we showed that let-7a, a member of let-7 family, negatively regulated the expression of NIRF through NIRF 3′ UTR. We also showed that NIRF was required for the let-7a-mediated elevation of p21WAF1. These findings suggest that growth-inhibitory effect of let-7a on the A549 cells in vitro and in vivo may be explained in part by le-7a-induced suppression of NIRF and elevation of p21WAF1. This work reveals a novel regulatory mechanism for let-7a in the control of cellular proliferation and lung carcinogenesis. [Copyright &y& Elsevier]

Numerous studies on carcinoma have revealed that the expression level of HOXB7 in cancerous tissues was significantly higher than that in noncancerous tissues. Elevated expression of HOXB7 is associated with the susceptibility to lymph node metastasis and distant metastasis in various tumors. In this study, a meta-analysis was performed to involve majority of relevant articles and explore the association of HOXB7 expression level with metastasis in cancer patients. Literature retrieval was conducted by searching in a number of electronic databases (up to December 1, 2015). The meta-analysis was conducted with RevMan 5.3 software and Stata SE12.0. A total of 1,532 patients with carcinoma from 14 studies were included in analysis. The results of meta-analysis demonstrated that lymph node metastasis was observed more frequently in the patients group with high expression level of HOXB7 than in the patients group with low expression level of HOXB7 (odds ratio =2.17, 95% CI: 1.74-2.71, P<0.00001, fixed-effects model). In addition, a similar result was observed in the association between HOXB7 expression and distant metastasis; the odds ratio was 1.77 (95% CI: 1.09-2.88, P=0.02, fixed-effects model). This meta-analysis demonstrated that the overexpression of HOXB7 was significantly associated with metastasis in cancer patients, which may be served as a common molecular marker for indicating cancer metastasis.

Introduction: Recent studies have reported that long non-coding RNA low expression in tumor (lncRNA-LET) was down-regulated in several cancers. The current meta-analysis aims to determine whether lncRNA-LET can be used as a potential biomarker for metastasis and prognosis., Evidence Acquisition: We collected all relevant papers by searching multiple electronic databases (PubMed, EMBASE, Google Scholar, CNKI, Wanfang Database) and explored the association between the expression levels of lncRNA-LET and lymph node metastasis (LNM), distant metastasis (DM) and overall survival (OS)., Evidence Synthesis: A total of 383 patients from four studies were finally included. The meta-analysis results showed that LNM occurred more frequently in patients from the lncRNA-LET low expression group than in patients from the lncRNA-LET overexpression group (OR=4.56, 95% CI 2.92-7.12, P<0.00001), and a similar result was observed between lncRNA-LET expression and DM (OR=4.77, 95% CI 2.29-9.94, P<0.0001). Additionally, we found that patients with low expression of lncRNA-LET had a poorer OS than those with lncRNA-LET overexpression (HR=2.39, 95% CI 1.57-3.21, P=0.000)., Conclusions: lncRNA-LET may serve as a common molecular marker for metastasis and prognosis in human cancers.

Introduction: The association between IL-16 rs1131445 polymorphism and cancer risk is not consistent or even contradictory, this meta-analysis aims to investigate the role of IL-16 gene rs1131445 polymorphisms in the risk of cancer., Evidence Acquisition: A comprehensive online search was conducted in PubMed, EMBASE and CNKI databases to identify eligible studies. The case-control studies related IL-16 rs1131445 C/T polymorphism with the cancer susceptibility were selected according to the inclusion and exclusion criteria. After extracting the basic data information and quality of literature evaluation, the meta-analysis was performed by using STATA 12.0 software, with calculating odds ratio and 95% confidence interval, and further subgroup analysis, literature publication bias test and sensitivity analysis., Evidence Synthesis: There are totally 1677 cases and 1989 non-tumor controls finally involved. Meta-analysis showed that there are statistical correlations between the IL-16 rs1131445 C/T polymorphism and the cancer risk in Asian populations (TS vs. C, OR=0.80, 95%CI: 0.73-0.88; TT vs. TC, OR=0.75, 95%CI: 0.65-0.87; TT vs. CC, OR=0.69, 95% CI: 0.56-0.84; CC+TC vs. TT, OR=1.36, 95%CI: 1.19-1.55; CC vs. TC+TT, OR=1.27, 95%CI: 1.05-1.53) (all P<0.05)., Conclusions: IL-16 rs1131445 C/T polymorphism is related to the susceptibility to cancer in Asians, suggesting that the C allelic gene of rs1131445 is significantly associated with an increasing cancer risk.

Objective: To elucidate the role of let-7a-mediated gene regulation in the pathogenesis of lung cancer., Methods: Two template DNA sequences were designed based on hsa-let-7a sequence in miRBase database. The let-7a expression construct and a control plasmid, namely pGenesil-let-7a and pGenesil-control, respectively, were generated by cloning the annealed oligonucleotides into pGenesil-1 and then transfected into A549 cells, which were selected by G418 to establish the lung cancer cell lines stably expressing let-7a-GFP and control-GFP. The living cells were counted by MTT assay and cell growth curves were drawn to analyze the cell proliferation. The k-Ras mRNA level was assessed by semi-quantitative RT-PCR, and the expression of k-Ras protein was determined by Western blotting and immunocytochemistry., Results: The recombinant vectors were verified by sequencing. The cell growth curves indicated that the proliferation of the cells transfected with pGenesil- let-7a were inhibited significantly compared with that of cells transfected with pGenesil-control and A549 cells. Semi- quantitative RT-PCR analysis showed that the levels of k-Ras mRNA almost remained unchanged in cells with or without the treatments. Western blotting and immunocytochemistry demonstrated a significant decrease of k-Ras protein levels in cells transfected with pGenesil-let-7a, but not in cells transfected with pGenesil-control, when compared to A549 cells., Conclusion: let-7a over-expression represses the expression of k-Ras protein and significantly inhibits the growth of lung cancer cells.

Objective: To investigate positron-emission tomography-computed tomography (PET/CT) findings of radiation encephalopathy (RE) following radiotherapy for nasopharyngeal carcinoma (NPC), observe the metabolic changes of the compromised brain tissues, and postulate the clinical classification of RE to provide reference for its diagnosis., Methods: This study included 53 pathologically confirmed NPC patients who received previous radical radiotherapy, and the diagnosis of RE was established according to the clinical manifestations and CT/PET findings. All the patients underwent PET/CT whole-body and head scans, and the image data were evaluated along with the clinical data of the patients., Results: RE most frequently involved the lateral or bilateral inferior temporal lobes. PET identified hypometabolic changes in the bilateral temporal lobes of 35 patients (70 lobes) and in the lateral temporal lobe of 18 patients (18 lobes). According to the PET/CT findings, the lesions were classified into 3 types, namely the oedema type (56 temporal lobes), liquefactive necrosis type (10 temporal lobes), and atrophic calcification type (22 temporal lobes). One patient with oedema type lesion received neurotrophic treatment and recovered completely with normal brain tissue density and metabolism, but the oedema type lesions in 2 patients progressed into to atrophic calcification type; the liquefactive necrotic lesions in another 2 patients also progressed into atrophic calcification type., Conclusion: RE patients exhibit significant hypometabolic changes in the inferior temporal lobe on PET. According to the findings by PET/CT, RE can be classified into the oedema type, liquefactive necrosis type, and atrophic calcification type, and lesions of the former two types may progress into the third type.