ABSTRACT
Mutation and amplification of epidermal growth factor receptor (EGFR), one of the most important driver gene, are both reported to participate in the regulation of lung cancer development and progression. Here we investigated the effect and molecular mechanism of tripartite motif 25 (TRIM25) in the regulation of development of lung cancer. CCK-8 and Transwell assays were used to explore the tumor-promoting effect of TRIM25. Results showed that knockdown of TRIM25 significantly inhibited cell proliferation (34% inhibition rate) and invasion (42% inhibition rate). Gene set enrichment analysis (GSEA), Western blot and immunohistochemistry were adopted to detect the effect of TRIM25 on EGFR expression and its downstream signal activity. The results explained that TRIM25 not only up-regulated the expression level of EGFR, but also promoted EGFR signal activation. Co-immunoprecipitation, real-time PCR and cycloheximide (CHX) inhibit protein degradation assays were employed to explore the molecular mechanism of TRIM25 in regulating EGFR stability. Preliminary exploration results indicate that TRIM25 increases the expression level of EGFR and activates its downstream signaling activity through promoting K63-linked ubiquitination of EGFR. Restoration of EGFR expression rescues the phenotype of TRIM25 depletion. In A549 cells, overexpression of EGFR increased cell proliferation rate 1.5-fold and invasion rate 1.6-fold compared with knockdown of TRIM25 cells. Similarly, in H1975 cells, cell proliferation rate was enhanced 2-fold and invasion rate was improved 1.7-fold. These data suggest that TRIM25 promotes lung cancer development via maintaining EGFR stability and continuous EGFR signaling activation. The human lung cancer tissues were obtained from lung cancer patients at Cancer Hospital Chinese Academy of Medical Sciences. Informed consent was obtained from all participants in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee of the Cancer Hospital Chinese Academy of Medical Sciences.
ABSTRACT
Macrophage migration inhibitory factor (MIF) is a classical pro-inflammatory cytokine that plays an important role in the innate and adaptive immune regulation. In recent years, a large number of studies have demonstrated that the expression level of MIF is significantly increased in a variety of tumor tissues and MIF promotes the occurrence and development of tumors. MIF participates in the regulation of tumor growth, metastasis, angiogenesis, as well as induces and maintains the tumor microenvironment. Targeting MIF has been considered as a candidate strategy against cancer. In this review, the structural features, the signaling pathway, the biological functions of MIF are briefly outlined. Moreover, approaches that target MIF in the treatment of cancer are also summarized.
ABSTRACT
<p><b>OBJECTIVE</b>To study the relationship between spiral CT findings and histological differentiation and expressions of p53 and Ki67 in gastric carcinoma.</p><p><b>METHODS</b>Triphasic spiral CT was performed in 158 patients. CT findings included maximal diameter and thickness of tumor in three dimensional CT images, degree of enhancement, mucous situation, lymph nodes, and visceral metastasis were recorded. The expressions of p53 and Ki67 were detected with immunohistochemistry and reverse transcription polymerase chain reaction.</p><p><b>RESULTS</b>The thickness of tumor (chi2 = 5.554, P = 0.018), degree of enhancement (chi2 = 4.978, P = 0.026), and lymph nodes metastasis (chi2 = 6.061, P = 0.014) in the three dimensional CT images were significantly correlated with tumor histological differentiation. Lymph nodes metastasis was significantly correlated with the expression of p53 (chi2 = 5.028, P = 0.025). The expression of Ki67 was significantly correlated with the thickness of tumor (chi2 = 5.674, P = 0.017) and lymph nodes metastasis (chi2 = 5.028, P = 0.025).</p><p><b>CONCLUSION</b>Multi-slice CT is a simple and noninvasive technique, and can be used for assessing the histological differentiation of gastric cancer as well as the expressions of p53 and Ki67 before the operation.</p>