Association between the pri-miR-26a-1 rs7372209 C>T polymorphism and cancer susceptibility: multivariate analysis and trial sequential analysis.

MiR-26 has been suggested to play a tumor-suppressive role in cancer development, which could be influenced by the mutate pri-miR-26ª-1. Molecular epidemiological studies have demonstrated some inconsistent associations between pri-miR-26ª-1 rs7372209 C>T polymorphism and cancer risk. We therefore performed this meta-analysis with multivariate statistic method to comprehensively evaluate the associations between rs7372209 C>T polymorphism and cancer risk. Eleven publications involving 6,709 patients and 6,514 controls were identified. Multivariate analysis indicated that the over-dominant genetic model was most likely. Pooled results indicated no significant association in the overall population (CC+TT vs. CT: OR=1.08, 95%CI=0.96-1.22, P=0.20, I2=54.4%), as well as the subgroup analysis according to ethnicity, control source, tumor locations, and HWE status of controls. In addition, heterogeneity, accumulative, sensitivity analysis, publication bias and trial sequential analysis (TSA) were conducted to test the statistical power. Overall, our results indicated that the pri-miR-26a-1 rs7372209 C>T polymorphism may not be a potential risk for cancer development.

Curcumin potentiates laryngeal squamous carcinoma radiosensitivity via NF-ΚB inhibition by suppressing IKKγ expression.

Context: Curcumin has shown efficacy in promoting radiosensitivity combined with radiotherapy. However, the role and mechanism of curcumin on radiosensitivity in laryngeal squamous cell cancer (LSCC) is largely unknown.Objective: The aim of our study is to explore the role of IKKγ-NF-κB signaling in curcumin enhancing LSCC cell radiosensitivity in vitro.Materials and methods: Curcumin and X-ray were used to induce cell DNA damage and apoptosis, or inhibit cell clone formation. IKKγ siRNA and plasmid were used to change IKKγ expression. The CCK8 assay was used to detect cell viability. Clone formation ability was analyzed using a clonogenic assay, cell apoptosis was examined using flow cytometry, an immunofluorescence assay was used to detect DNA damage, while mRNA and protein levels were assayed using real time PCR and western blotting, respectively.Results: Curcumin significantly enhanced irradiation-induced DNA damage and apoptosis, while weakening clone-forming abilities of LSCC cell line Hep2 and Hep2-max. Compared to Hep2 cells, Hep2-max cells are more sensitive to curcumin post-irradiation. Curcumin suppressed irradiation-induced NF-κB activation by suppressing IKKγ expression, but not IKKα and IKKß. Overexpression of IKKγ decreased irradiation-induced DNA damage and apoptosis, while promoting clone-forming abilities of Hep2 and Hep2-max cells. IKKγ overexpression further increased expression of NF-κB downstream genes, Bcl-XL, Bcl-2, and cyclin D1. Conversely, IKKγ silencing enhanced irradiation-induced DNA damage and apoptosis, but promoted clone formation in Hep2 and Hep2-max cells. Additionally, IKKγ silencing inhibited expression of Bcl-XL, Bcl-2, and cyclin D1.Conclusions: Curcumin enhances LSCC radiosensitivity via NF-ΚB inhibition by suppressing IKKγ expression.

Radiosensitisation of human glioma cells by inhibition of ß1,6-GlcNAc branched N-glycans.

Gliomas are the most prevalent type of primary brain tumors and are resistant to radiation therapy. ß1,6-GlcNAc branched N-glycans, which are encoded by N-acetylglucosaminyltransferase V (GnT-V), play important roles in glioma progression. However, the relationship between ß1,6-GlcNAc branched expression and radiosensitivity in glioma cells is still unknown. In this study, the expression of ß1,6-GlcNAc branched N-glycans in nonneoplastic brain and glioma samples was characterized by lectin histochemistry. The radiosensitivity of glioma cells was evaluated by colony formation assay. We found that ß1,6-GlcNAc branches were highly expressed in glioblastoma specimens, compared with diffuse astrocytomas and nonneoplastic brain. In addition, ß1,6-GlcNAc branched expression was negatively correlated with the radiosensitivity of glioblastoma cells. Furthermore, the inhibition of N-linked ß1,6-GlcNAc branches by GnT-V silencing in U251 cells could reduce the cell clonogenic survival after X-irradiation. Meanwhile, the G2/M checkpoint was impaired and there was an increase in the number of apoptotic cells. Tunicamycin, an inhibitor of N-glycan biosynthesis, was also able to enhance the radiosensitivity of U251 cells. Thus, our results suggest that development of therapeutic approaches targeting N-linked ß1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment.

Reversal effect of GnT-V on the radioresistance of human nasopharyngeal carcinoma cells by alteration ß1, 6-GlcNAc branched N-glycans.

Radiotherapy is the primary treatment for human nasopharyngeal carcinoma (NPC), yet radioresistance remains a major obstacle to successful treatment in many cases. N-acetylglucosaminyltransferase V (GnT-V), which synthesizes ß1, 6-GlcNAc branched N-glycans, is closely related to the radiosensitivity of NPC cells. However, a better understanding of the functional role of GnT-V in NPC radioresistance and the related mechanisms is urgently needed. In the present study, a radioresistant NPC cell line, CNE-2R, was established by repeated γ-irradiation. We found that GnT-V levels, as well as ß1, 6-GlcNAc branched N-glycans were significantly increased in the CNE-2R cells as compared with that in the parental cells. Meanwhile, knockdown of GnT-V in the CNE-2R cells enhanced cell radiosensitivity and inhibited the formation of ß1, 6-branched N-glycans. In addition, the regulated expression of GnT-V in the CNE-2R cells converted the heterogeneous N-glycosylated forms of CD147. Furthermore, swainsonine, an inhibitor of N-glycan biosynthesis, was also able to reverse the radioresistance of the CNE-2R cells. Taken together, the present study revealed a novel mechanism of GnT-V as a regulator of radioresistance in NPC cells, which may be useful for fully understanding the biological role of N-glycans in NPC radioresistance.