Role of B7-H4 siRNA in Proliferation, Migration, and Invasion of LOVO Colorectal Carcinoma Cell Line

Peng, Haixia; Wu, Weiqi; Yang, Dian; Jiang, Rong; Li, Ji; Zhou, Fengli; Jin, Yunfei; Wang, Sai-yu; Chu, Yi-Min

doi:10.1155/2015/326981

Cited by 26 publications

(25 citation statements)

References 19 publications

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“…This suggests that B7-H3 has a putatively important role in tumor migration and invasiveness, indicating higher aggressiveness and poor clinical outcome. Besides, we found that ESCC cell growth could be inhibited after B7-H4 knockdown, which was consistent with Peng et al report [43]. These results suggest that interference with the mediated T cell costimulatory signal transduction pathway by blocking B7-H3 and/or B7-H4 pathway may lead to future immunological therapeutics for the treatment of ESCC via different mechanisms.…”

Section: Discussionsupporting

confidence: 91%

Roles of coinhibitory molecules B7-H3 and B7-H4 in esophageal squamous cell carcinoma

et al. 2015

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The coinhibitory molecules, B7-H3 and B7-H4, have shown negative regulation in T cell activation and tumor-associated macrophage (TAM) polarization in tumor-specific immunity. Here, we investigated the expression of B7-H3 and B7-H4 in human and murine esophageal squamous cell carcinoma (ESCC) tissues to define their clinical significance and mechanism in a tumor microenvironment. In the present study, B7-H3 and B7-H4 were expressed in 90.6 and 92.7 % samples, respectively. High B7-H3 and B7-H4 expression was associated with advanced TNM stage and lymph node metastasis (p < 0.05, respectively). Patients with both B7-H3 and B7-H4 high-expressed tumors had the poorest prognosis (26.7 months), whereas those with both low-expressed tumors had the best survival (56.7 months). B7-H3 and B7-H4 expression were inclined to be positively related to the infiltration intensity of Treg cells and TAMs (p < 0.05, respectively), and B7-H3 expression is negatively associated with the intensity of CD8(+) T cells (p < 0.05). In 4-nitroquinoline 1-oxide (4-NQO)-induced murine models, high B7-H3 expression could only be detected at carcinoma stage, but abnormal B7-H4 expression appeared a little earlier at dysplasia stage. In vitro studies revealed that knockdown of B7-H3 on tumor cells suppressed ESCC cell migration and invasion, while knockdown of B7-H4 could inhibit ESCC cell growth. Overall, B7-H3 and B7-H4 are involved in ESCC progression and development and their coexpression could be valuable prognostic indicators. Interference of these negative regulatory molecules might be a new strategy for treating ESCC.

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Section: Discussionsupporting

confidence: 91%

Roles of coinhibitory molecules B7-H3 and B7-H4 in esophageal squamous cell carcinoma

et al. 2015

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“…B7-H4 was also involved in the regulation of cancer cell behaviors such as proliferation, cell cycle arrest, migration and invasion. The gene set enrichment analysis showed that CXCL12/CXCR4 and JAK/STAT pathways were correlated with the B7-H4 expression [31]. …”

Section: Discussionmentioning

confidence: 99%

Assessment of combined expression of B7-H3 and B7-H4 as prognostic marker in esophageal cancer patients

et al. 2016

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The co-stimulatory ligands of B7-family have been confirmed to play an important role in negatively regulating the T-cell mediated anti-tumor immunity. In addition, these inhibitory molecules are also aberrantly expressed on various human cancers tissues, and significantly associated with cancer progression and patients' poor prognoses. We have previously reported that B7-H3 and B7-H4 ligands are highly expressed in human esophageal cancer tissues. Herein, we tried to further analyze the value of their combined expression on prognostic prediction for esophageal cancer patients. We found that the combined expression of both B7-H3 and B7-H4 could be used as a valuable risk factor for predicting the prognosis of esophageal cancer patients (P=0.003). Moreover the status of these patients with high expression of both B7-H3 and B7-H4, was positively and significantly associated with the tumor invasion depth (P=0.0414) and TNM stage (P=0.0414). The Cox multivariate proportional hazards regression analysis revealed that the tumor size (P=0.007), the TNM stage (P=0.024) and the status of both B7-H3 and B7-H4 high expression (P=0.011), could be used as an independent risk factor for predicting patients' postoperative prognosis, respectively. In conclusion, our data indicated that the combined application of B7-H3 and B7-H4 expression can be effectively used as a prognostic marker in esophageal cancer patients.

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“…The Western blot analysis was carried out as described previously . The transfer times were: 30 min for GAPDH, TATA‐binding protein (TBP), Bcl‐2, BAX, and Survivin; 1 h for B7‐H4, STAT3, and p‐STAT3; and 2 h for JAK2 and p‐JAK2.…”

Section: Methodsmentioning

confidence: 99%

B7‐H4 facilitates proliferation of esophageal squamous cell carcinoma cells through promoting interleukin‐6/signal transducer and activator of transcription 3 pathway activation

Chen

Wang

et al. 2016

Cancer Science

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B7‐H4, one of the costimulatory molecules of the B7 family, has been found to be widely expressed in many kinds of tumor tissues and to play an important part in tumor progression and poor prognosis. However, the role of B7‐H4 in esophageal squamous cell carcinoma (ESCC) cells has not been elucidated. In this study, we found that, compared with normal esophageal tissue, B7‐H4 was highly expressed in three ESCC cell lines, Eca109, TE1, and TE13. B7‐H4 silenced cells suppressed cellular proliferation and colony formation. Additionally, compared with control cells, B7‐H4 silenced cells showed higher apoptosis rates, Bcl‐2 and Survivin upregulation, and BAX downregulation. Further study revealed that B7‐H4 silenced cells also showed reduction in interleukin‐6 (IL‐6) secretion, signal transducer and activator of transcription 3 (STAT3) activation, and p‐STAT3 translocation from cytoplasm to nucleus. Moreover, B7‐H4 depletion inhibited the IL‐6 secretion of control cells but not JAK2/STAT3 inhibitor FLLL32‐treated cells. Interleukin‐6 receptor antagonist tocilizumab did not block the p‐JAK2 or p‐STAT3 downregulation induced by B7‐H4 silence. It was suggested that B7‐H4 silence suppressed IL‐6 secretion through JAK2/STAT3 inactivation. Furthermore, cell proliferation and colony formation were downregulated by tocilizumab in control cells but not in B7‐H4 silenced cells, indicating that IL‐6 upregulation induced by B7‐H4 was necessary for cell growth. On the other hand, B7‐H4 expression was downregulated by tocilizumab. In all, our study provided the first evidence that B7‐H4 facilitated ESCC cell proliferation through promoting IL‐6/STAT3 positive loopback pathway activation.

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Role of B7-H4 siRNA in Proliferation, Migration, and Invasion of LOVO Colorectal Carcinoma Cell Line

Cited by 26 publications

References 19 publications

Roles of coinhibitory molecules B7-H3 and B7-H4 in esophageal squamous cell carcinoma

Roles of coinhibitory molecules B7-H3 and B7-H4 in esophageal squamous cell carcinoma

Assessment of combined expression of B7-H3 and B7-H4 as prognostic marker in esophageal cancer patients

B7‐H4 facilitates proliferation of esophageal squamous cell carcinoma cells through promoting interleukin‐6/signal transducer and activator of transcription 3 pathway activation

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