Osteosarcoma (OS) is the most common primary malignancy of the bone affecting children and adolescents. Copine 1 (CPNE1) is a highly conserved calcium-dependent phospholipid-binding protein and may function in regulating signal transduction and membrane trafficking. In the present study, we investigated CPNE1 expression in osteosarcoma tissues and cells, and studied the effects of small interfering RNA (siRNA)-targeting CPNE1 on proliferation, metastasis and chemosensitivity of the osteosarcoma cells. The results demonstrated that CPNE1 was highly expressed in the osteosarcoma tissues and cell lines. Moreover, functional investigations confirmed that CPNE1 knockdown significantly inhibited cell proliferation, colony formation, invasion and metastasis in Saos-2 and HOS cells. Western blot analysis indicated that CPNE1 silencing downregulated the expression of many proteins associated with tumorigenesis and development, including Ras, MEK-1/2, WNT1, β-catenin, cyclin A1, IRAK2 and cIAP2. In addition, CPNE1 downregulation enhanced the sensitivity of Saos-2 cells towards cisplatin and adriamycin. The present study provides deep insight into the clinical use of lentiviral-mediated CPNE1 silencing for osteosarcoma therapy.

The ACTN3 577X allele is associated with an age- and sex-specific decrease in physical performance and an increase in frailty in an older population.

Abstract. The family of semaphorins has been demonstrated to possess tumor suppressor activity, in which semaphorin 3B (SEMA3B) is differentially expressed in several types of tumors. The relationship between SEMA3B expression and its clinical significance in gastric cancer (GC) is currently unclear. In the present study, the expression and methylation status of the SEMA3B gene were detected by quantitative PCR and bisulfite sequencing PCR (BSP). Data indicated that the levels of SEMA3B mRNA decreased in gastric tumor tissues and the methylation status of SEMA3B in the tumor group was higher than the paired normal tissues. By BSP, the SEMA3B gene showed high methylated status which was detected in all 4 cell lines (AGS, BGC-823, MGC-803 and SGC-7901). Treatment of the cells with 5-Aza-2'-deoxycytidine revealed clearly elevated mRNA levels of SEMA3B. These results were further confirmed by western blot analysis of Sema3b protein expression. At the same time, increased expression of p53 mRNA in BGC-823, MGC-803 was detected and indicated that p53 may be involved in the regulation of SEMA3B expression in specific genetic background. Downregulation of SEMA3B was negatively correlated with tumor size and N staging in GC (P<0.05). In conclusion, CpG methylation of SEMA3B epigenetically regulates SEMA3B expression during development of GC. Furthermore, 5-Aza-2'-deoxycytidine could reverse the hypermethylation status of SEMA3B, which may benefit future studies exploring the application of demethylating agents in clinical usage of GC.

Hypoxia is a common phenomenon in the development of solid tumors, and hypoxia inducible factor 1 (HIF-1) plays a central role in coordinating the cellular response to hypoxia and in oxygen homeostasis. The prolyl hydrolase 1 (PHD1) is a key adjustment factor that mediates the HIF-1 degradation and relates with the process of tumorigenesis. Thus, polymorphism in PHD1 may affect cellular response to hypoxic conditions and associate with cancer susceptibility. We conducted a case-control study with 406 non-small cell lung cancer cases and 812 healthy controls matched on age and sex to examine the effect of rs10680577 polymorphism within the PHD1 promoter on non-small cell lung cancer (NSCLC) risk in a Chinese population. The genotype of rs10680577 polymorphism was detected by non-denaturing polyacrylamide gel electrophoresis. The ins/del genotype of rs10680577 was associated with significantly increased non-small cell lung cancer risk (ins/del vs. ins/ins: OR = 1.35, 95 % confidence interval (CI) 1.05-1.74, P = 0.020; ins/del vs. ins/ins + del/del: OR = 1.34, 95 % CI = 1.04-1.72, P = 0.022). In addition, the association was more pronounced in the group of >60 years of age. rs10680577 polymorphism is associated with the risk of non-small cell lung cancer in a Chinese population. This is the first time to show that PHD1 rs10680577 is associated NSCLC risk.

Cytokines are vital mediators involved in tumor immunity. We aimed to explore whether the expression levels of IL-1β, TNF-α and IL-6 have impacts on prognosis of SCLC patients. In this study, we concluded 707 non-operable SCLC patients at stage III or IV into this study and analyzed the relationships between interleukins and OS/PFS by cox regression analysis and Kaplan-Meier analysis (log-rank test). As a result, under current standard chemotherapy, SCLC patients with higher IL-6 expression level had a shortened OS compared with those with normal level (HR: 0.381, 95%CI: 0.177-0.822, p=0.014). Furthermore, IL-6 expression level contributed mostly to patients without a smoking history. Non-smoking patients with a high IL-6 level showed a 6 months shortened OS than those with normal IL-6 level (10.50 vs 16.90 months, p=0.003 by Log-Rank test in Kaplan-Meier analysis). IL-6 had no obvious impacts on first-line PFS in these SCLC patients. To conclude, IL-6 acts as an independent factor of long-term prognosis of SCLC patients under current therapy.