BackgroundWe have preliminarily reported MTA2 expression in gastric cancer and its biological functions by using knockdown cell models, while the molecular mechanisms of MTA2 in regulating malignant behaviors are still unclear.MethodsMTA2 overexpression models were established by transfection assay in gastric cancer cells BGC-823 and MKN28. Cell proliferation assay, colony formation in soft agar, wound-healing assay and transwell migration assay were performed with MTA2 overexpression and negative control (NC) cells. Subcutaneous xenografts and pulmonary metastasis models by BGC-823/MTA2 and BGC-823/NC cells were used to observe the capacity of growth and metastasis in vivo. Differential gene expression in MTA2 knockdown and overexpression cells was analyzed by microarrays. IL-11, which demonstrated as differential expression in microarray, was detected by real-time PCR, western blot, ELISA and immunohistochemistry staining. Recombinant human IL-11 (rhIL-11) was administrated in cell proliferation and colony formation as rescue assay.ResultsThe numbers of colonies in soft agar were significantly more in BGC-823/MTA2 and MKN28/MTA2 cells, comparing with those in their NC cells. Capabilities of cell proliferation, wound-healing and cell migration were not significantly changed in MTA2 overexpression cells. The sizes of subcutaneous xenografts and pulmonary metastases of BGC-832/MTA2 cells were significantly larger than those in BGC-823/NC group. Differential expression of IL-11 was identified by genome expression microarray both in MTA2 knockdown and overexpression cells. IL-11 expression was elevated in BGC-823/MTA2 cells, whereas reduced in SGC-7901/shMTA2 cells. Administration of rhIL-11 recovered colony formation capacity of SGC-7901/shMTA2 cells.ConclusionsMTA2 overexpression enhances colony formation and tumor growth of gastric cancer cells, but not plays important role in cancer cell migration and metastasis. IL-11 is one of the downstream effectors of MTA2 in regulating gastric cancer cells growth.

BackgroundThe fragile-site associated tumor suppressor (FATS, formerly known as C10orf90), a regulator of p53-p21 pathway has been involved in the onset of breast cancer. Recent data support the idea that the crosstalk between FATS and p53 may be of physiological importance for reproduction during evolution. The aim of the current study was to test the hypothesis that FATS genetic polymorphism can influence the risk of breast cancer.MethodsWe conducted population-based studies in two independent cohorts comprising 1 532 cases and 1 573 controls in Tianjin of North China, and 804 cases and 835 controls in Guangzhou of South China, coupled with functional validation methods, to investigate the role of FATS genetic variant in breast cancer risk.ResultsWe identified a functional variant rs11245007 (905C > T, 262D/N) in fragile-site gene FATS that modulates p53 activation. FATS-262 N exhibited stronger E3 activity to polyubiquitinate p53 than did FATS-262D, leading to the stronger transcriptional activity of p53 and more pronounced stabilization of p53 protein and its activation in response to DNA damage. Case–control studies found that CT or TT genotype was significantly associated with a protective effect on breast cancer risk in women with parity ≥ 3, which was not affected by family history.ConclusionsOur findings suggest the role of FATS-p53 signaling cascade in suppressing pregnancy-related carcinogenesis and potential application of FATS genotyping in breast cancer prevention.

s Background Esophageal cancer (EC) is one of the most common cancers worldwide. The cancer-related inflammation pathway- signal transducer and activator of transition 3 (STAT3) signaling pathway has been reported to play critical role in its initiation and progression, while the way mediated its hyperactivation remains elusive so far. Accumulating studies reported the important role of microRNAs (miRNAs) in the regulation of gene expression, among of which, the miR-124/STAT3 interaction has been widely reported in various cancers, while its role in EC has not been investigated yet. Methods Firstly, we identified the target role of STAT3 in esophageal cancers using Dual-luciferase reporter assays. Next, we explored the expression of miR-124 in EC tissues. To further investigate its effects on the malignant phenotype of EC cells, we completed a series of experiments. Through transfection with miR-124 mimic, the expression of miR-124 in esophageal cancer cell lines, Eca109 and TE-1, were restored. Next, we detected the effects of ectopic miR-124 expression on the proliferation, cell cycle distribution, apoptosis, migration and invasion of EC cells in vitro, and the tumor growth in vivo. Results Dual-luciferase assays identified that STAT3 is a target gene of miR-124 in esophageal cancer cells. Over-expression of miR-124 significantly down-regulated the mRNA and protein levels of STAT3. Moreover, we found that the expression of miR-124 was consistently suppressed in esophageal cancer tissues and cell lines. Next, functional experiments showed that ectopic expression of miR-124 in EC cells induced a complex phenotype, namely an inhibition of cell proliferation, block of G1/S phase transition, induction of cell apoptosis, and suppression of cell invasion in vitro, as well as inhibition of tumor growth in vivo. Moreover, restored the expression of STAT3 in esophageal cancer cells transfected with miR-124 before, could partially abolished the suppressive effects of miR-124 on the proliferation and invasion of Eca109 cells. Conclusion Collectively, these data suggest that miR-124 functions as a tumor suppressor in esophageal cancer through, at least partially, targeting STAT3 signaling pathway.

Background

CBX7 is a Polycomb group protein that shows variable expression changes in various cancers that are often contradictive. A mouse knockout experiment has validated the tumor suppressor role in carcinogenesis. The purpose of this study is to verify the tumor suppressor role of Cbx7 in human colon carcinomas (CC).

Methods

Frozen CC and the surgical margin (SM) tissue samples from patients (n = 97) were obtained from the Peking University Cancer Hospital. All patients had follow-up data for at least three years. The level of Cbx7 mRNA and protein was determined by quantitative RT-PCR, immunohistochemistry and Western blot, respectively. The association between Cbx7 mRNA level and clinicopathological characteristics of CC patients was then statistically analyzed.

Results

CBX7 expression changes detected through immunohistochemistry and Western blot in 10 pairs of representative CC samples significantly correlated with their corresponding mRNA levels when Alu, but not GAPDH, was used as the endogenous reference control in quantitative RT-PCR. The Alu-normalized Cbx7 mRNA levels were significantly increased in SM tissues when compared with CC tissues or colon biopsies taken from non-cancer patients (Student’s t-test, P < 0.036 or 0.007). Furthermore, decreased levels of Cbx7 mRNA positively correlated with lymph metastasis (P = 0.029). Overall survival (OS) of CC patients classified as Cbx7 expression-low was considerably shorter than those classified as Cbx7 expression-high (Hazard ratio = 2.97, 95% CI [1.68 ~ 5.25]; P <0.001). Multiple variant analyses showed that the Cbx7 expression-low was an independent predictor of short OS (Hazard ratio = 3.16, 95% CI [1.58-6.30]; P < 0.001).

Conclusion

Cbx7 is downregulated in CCs, and Cbx7 expression-low tumors correlated with lymph metastasis and poor overall survival of CC patients.

s Background Esophageal cancer (EC) is one of the most common cancers worldwide. The cancer-related inflammation pathway- signal transducer and activator of transition 3 (STAT3) signaling pathway has been reported to play critical role in its initiation and progression, while the way mediated its hyperactivation remains elusive so far. Accumulating studies reported the important role of microRNAs (miRNAs) in the regulation of gene expression, among of which, the miR-124/STAT3 interaction has been widely reported in various cancers, while its role in EC has not been investigated yet. Methods Firstly, we identified the target role of STAT3 in esophageal cancers using Dual-luciferase reporter assays. Next, we explored the expression of miR-124 in EC tissues. To further investigate its effects on the malignant phenotype of EC cells, we completed a series of experiments. Through transfection with miR-124 mimic, the expression of miR-124 in esophageal cancer cell lines, Eca109 and TE-1, were restored. Next, we detected the effects of ectopic miR-124 expression on the proliferation, cell cycle distribution, apoptosis, migration and invasion of EC cells in vitro, and the tumor growth in vivo. Results Dual-luciferase assays identified that STAT3 is a target gene of miR-124 in esophageal cancer cells. Over-expression of miR-124 significantly down-regulated the mRNA and protein levels of STAT3. Moreover, we found that the expression of miR-124 was consistently suppressed in esophageal cancer tissues and cell lines. Next, functional experiments showed that ectopic expression of miR-124 in EC cells induced a complex phenotype, namely an inhibition of cell proliferation, block of G1/S phase transition, induction of cell apoptosis, and suppression of cell invasion in vitro, as well as inhibition of tumor growth in vivo. Moreover, restored the expression of STAT3 in esophageal cancer cells transfected with miR-124 before, could partially abolished the suppressive effects of miR-124 on the proliferation and invasion of Eca109 cells. Conclusion Collectively, these data suggest that miR-124 functions as a tumor suppressor in esophageal cancer through, at least partially, targeting STAT3 signaling pathway.

Background

CBX7 is a Polycomb group protein that shows variable expression changes in various cancers that are often contradictive. A mouse knockout experiment has validated the tumor suppressor role in carcinogenesis. The purpose of this study is to verify the tumor suppressor role of Cbx7 in human colon carcinomas (CC).

Methods

Frozen CC and the surgical margin (SM) tissue samples from patients (n = 97) were obtained from the Peking University Cancer Hospital. All patients had follow-up data for at least three years. The level of Cbx7 mRNA and protein was determined by quantitative RT-PCR, immunohistochemistry and Western blot, respectively. The association between Cbx7 mRNA level and clinicopathological characteristics of CC patients was then statistically analyzed.

Results

CBX7 expression changes detected through immunohistochemistry and Western blot in 10 pairs of representative CC samples significantly correlated with their corresponding mRNA levels when Alu, but not GAPDH, was used as the endogenous reference control in quantitative RT-PCR. The Alu-normalized Cbx7 mRNA levels were significantly increased in SM tissues when compared with CC tissues or colon biopsies taken from non-cancer patients (Student’s t-test, P < 0.036 or 0.007). Furthermore, decreased levels of Cbx7 mRNA positively correlated with lymph metastasis (P = 0.029). Overall survival (OS) of CC patients classified as Cbx7 expression-low was considerably shorter than those classified as Cbx7 expression-high (Hazard ratio = 2.97, 95% CI [1.68 ~ 5.25]; P <0.001). Multiple variant analyses showed that the Cbx7 expression-low was an independent predictor of short OS (Hazard ratio = 3.16, 95% CI [1.58-6.30]; P < 0.001).

Conclusion

Cbx7 is downregulated in CCs, and Cbx7 expression-low tumors correlated with lymph metastasis and poor overall survival of CC patients.