Metastasis-Associated in Colon Cancer-1 Associates With Poor Prognosis and Promotes Cell Invasion and Angiogenesis in Human Cervical Cancer.

OBJECTIVE: The aim of this study is to investigate the clinicopathologic significance and potential role of metastasis-associated in colon cancer-1 (MACC1) in the progression of cervical cancer. METHODS: MACC1 expression was examined in cervical cancer cell lines, 6 matched cervical cancer tissues, and adjacent noncancerous tissues using Western blotting and real-time reverse transcriptase polymerase chain reaction. MACC1 protein expression and localization were determined in 181 paraffin-embedded archived cervical cancer samples using immunohistochemistry. Statistical analyses were applied to evaluate the clinicopathologic significance. The effects of MACC1 on cell migration, invasion, and angiogenesis were examined using migration assay, wound healing assay, 3-dimensional morphogenesis assay, and chicken chorioallantoic membrane assay. Western blotting was performed to examine the impact of MACC1 on the Akt and nuclear factor κB signaling pathways. RESULTS: Both protein and messenger RNA levels of MACC1 was up-regulated in cervical cancer cell lines and cervical cancer tissues, as compared with normal tissues. High MACC1 expression was detected in 96 (53%) of 181 of the cervical cancer tissues. In addition, high MACC1 expression correlated significantly with aggressiveness of cervical cancer, including International Federation of Gynecology and Obstetric stage (P = 0.001), pelvic lymph node metastasis (P = 0.004), recurrence (P = 0.037), and poor survival (P = 0.001). Moreover, enforced expression of MACC1 in cervical cancer cell lines significantly enhanced cell migration, invasion, and angiogenesis. Conversely, knockdown of MACC1 caused an inhibition of cell migration, invasion, and angiogenesis. Up-regulation of MACC1 increased, but knockdown of MACC1 decreased the expression of matrix metalloproteinase-2 and matrix metalloproteinase-9. Furthermore, enforced expression of MACC1 could enhance, but knockdown of MACC1 could reduce AKT and nuclear factor κB pathway activity. CONCLUSIONS: Our findings suggest that MACC1 protein, as a valuable marker of cervical cancer prognosis, plays an important role in the progression of human cervical cancer cells.

Association study of a single nucleotide polymorphism in the exon 2 region of toll-like receptor 9 (TLR9) gene with susceptibility to systemic lupus erythematosus among Chinese.

Toll-like receptor 9 (TLR9) plays an important role in the induction and regulation of the innate immune system or adaptive immune responses. Genetic variations within human TLR9 have been reported to be associated with a range of immune-related diseases, such as asthma, systemic lupus erythematosus (SLE) and so on. Family-based association analysis was performed to further investigate whether a single nucleotide polymorphism (rs352140) in the exon 2 region of TLR9 gene is associated with susceptibility to SLE in a Chinese population. A total of 77 patients with SLE from 74 nuclear families, aged from 12 to 63 years, were enrolled according to 1997 criteria of American College of Rheumatology (ACR), 211 family members of these patients were also included. Genotyping was performed by PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Among 77 patients with SLE, the CC, CT and TT genetype frequencies of the SNP (rs352140) were 20.8, 61.0 and 18.2%, respectively. Single loci analysis suggested that the T allele at position of rs352140 was significantly associated with the susceptibility to SLE (Z = 2.357, P = 0.018402) in dominant model, but not in additive or recessive model. Genetype analysis showed that individuals with CT genetype had greater susceptibility to SLE than those without (Z = 2.004, P = 0.045067). Our study suggests that a single nucleotide polymorphism (rs352140) in the exon 2 region of TLR9 gene may be a susceptibility factor for SLE in Chinese population.