Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor-induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin-like growth factor-1 (IGF-1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF-1-dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown. In the study, we demonstrated a significant association between C1QBP expression and hepatic metastasis in patients with pancreatic cancer. IGF-1 induced the translocation of C1QBP from cytoplasm to lipid rafts and further drove the formation of CD44 variant 6 (CD44v6)/C1QBP complex in pancreatic cancer cells. C1QBP interacting with CD44v6 in lipid rafts promoted phosphorylation of IGF-1R and thus activated downstream PI3K and MAPK signaling pathways which mediated metastatic potential of pancreatic cancer cells including proliferation, apoptosis, invasion, adhesion and energy metabolism. Furthermore, C1QBP knockdown suppressed hepatic metastasis of pancreatic cancer cells in nude mice. We therefore conclude that C1QBP in lipid rafts serves a key regulator of IGF-1/IGF-1R-induced hepatic metastasis from pancreatic cancer. Our findings about C1QBP in lipid rafts provide a novel strategy to block IGF-1/IGF-1R signaling in pancreatic cancer and a reliable premise for more efficient combined modality therapies.

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Small cell carcinoma (SCC) is a malignant epithelial tumor that predominantly arises in the lungs. Primary SCC of the parotid gland is rare and difficult to diagnose by analysis of frozen sections obtained during surgery. Due to the aggressive nature of SCC and the frequent occurrence of distant metastases, identification of the disease is important. The current study reports the case of a male patient who presented with a right parotid gland mass. The tumor was resected and evaluated by light microscopy and immunohistochemical analysis. Immunohistochemically, the tumor was positive for cytokeratin, epithelial membrane antigen, cluster of differentiation 117, synaptophysin and thyroid transcription factor-1, which indicated that the tumor was a SCC of the parotid gland. An extended resection of the right parotid gland mass and dissection of the facial nerve were performed. Following discharge from the hospital, the patient received radiation therapy postoperatively. The patient has remained disease free during five months of follow-up.

This study aimed at determining the role of hsa-let-7e-5p in the progression of head and neck squamous cell carcinoma (HNSCC). The relative levels of hsa-let-7e-5p transcripts in 15 paired of HNSCC and adjacent non-tumor tissues and cells were examined by quantitative real-time PCR (qRT-PCR). The potential targets of hsa-let-7e-5p were predicted and validated by luciferase assay. The impact of altered hsa-let-7e-5p expression on HNSCC cell proliferation and metastasis was determined by CCK-8, wound healing, transwell migration and invasion assays. The effect of hsa-let-7e-5p over-expression on the growth of HNSCC was examined in vivo . Hsa-let-7e-5p expression was significantly down-regulated in HNSCC tissues and highly metastatic PCI-37B cells. Bioinformatic analysis predicted that hsa-let-7e-5p bound to the 3'untranslated region (3'UTR) of chemokine receptor 7(CCR7), which was validated by luciferase assay. While transfection with hsa-let-7e-5p mimic significantly decreased CCR7 protein expression, transfection with hsa-let-7e-5p inhibitor increased CCR7 protein expression in HNSCC cells. Similarly, hsa-let-7e-5p over-expression inhibited PCI-37B cell proliferation, wound healing, migration and invasion, while inhibition of endogenous hsa-let-7e-5p had opposite effects in PCI-37A cells. Hsa-let-7e-5p over-expression inhibited PCI-37B tumor growth in vivo . Therefore, hsa-let-7e-5p acts as a tumor suppressor to inhibit the progression of HNSCC by targeting CCR7 expression. Hsa-let-7e-5p and CCR7 may be therapeutic targets of HNSCC.

MicroRNAs (miRNAs) play important roles in regulation of proliferation, migration, and invasion of head and neck squamous cell carcinoma (HNSCC). The present study assessed expression, functions and mechanisms of miR‑20a‑5p in the regulation of HNSCC cell proliferation, migration and invasion. miR‑20a‑5p expression in HNSCC cell lines and tissues was detected using qRT‑PCR, while miR‑20a‑5p mimics and inhibitor were transfected into HNSCC cells for assessment of the effects using different assays (CCK‑8, wound healing and Transwell assays) and expression of miR‑20a‑5p‑targeting genes (using western blot and luciferase reporter assays). The data revealed that miR‑20a‑5p was upregulated in both HNSCC tissues and metastatic HNSCC cells. Upregulated miR‑20a‑5p expression in HNSCC cells promoted tumor cell proliferation, migration and invasion capacities, but resulted in downregulation of TNFRSF21 expression and in turn upregulation of C‑C motif chemokine receptor 7 (CCR7) in HNSCC cells. Concordantly, knockdown of miR‑20a‑5p in HNSCC had the opposite results. In conclusion, miR‑20a‑5p functioned as an oncogene in HNSCC by downregulating TNFRSF21 and subsequently, upregulating CCR7 expression.

Head and neck squamous cell carcinoma (HNSCC) is usually diagnosed accompanied by lymph node metastasis. C-C chemokine receptor type 7 (CCR7) is associated with the invasion and metastasis of tumors in HNSCC through various signaling pathways. The role of hsa-miR-125a-5p in HNSCC remains unclear. The present study was performed to investigate the association between hsa-miR-125a-5p and CCR7 in HNSCC. Reverse transcription-quantitative polymerase chain reaction was applied to analyze the expression of hsa-miR-125a-5p in clinical samples. Cell Counting Kit-8, Transwell and wound healing assays were used to detect cell proliferation, invasion, and metastasis, respectively, following overexpression of hsa-miR-125a-5p. Changes in protein expression of CCR7 were observed using western blotting. In the survival analysis, Student's t-tests and log rank tests were performed to analyze the association between the expression of hsa-miR-125a-5p, and HNSCC according to the Cancer Genome Atlas database. The expression of hsa-miR-125a-5p was identified to be significantly lower in cancer tissue compared with the corresponding adjacent normal tissues in clinical samples (P=0.038). The results of western blotting indicated that there was a positive regulatory association between hsa-miR-125a-5p and CCR7. Furthermore, overexpression of hsa-miR-125a-5p significantly enhanced the ability of cell proliferation, migration and invasion in HNSCC, with upregulation of CCR7. The results of survival analysis revealed that patients in the low expression group of hsa-miR-125a-5p tended to have longer survival times compared with the high expression group (P=0.045). Altogether, the data raised the possibility that hsa-miR-125a-5p has a significant role in promoting cancer in HNSCC, which may provide a basis for the treatment of HNSCC in molecular targeted therapy. Further studies are required to ascertain the role of hsa-miR-125a-5p in other HNSCC cell lines and in vivo.

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In this study we report a novel specificity protein 1 (SP1)/microRNA-92b (miR-92b) feedback loop regulating the migration and invasion of head and neck squamous cell carcinoma (HNSCC). Microarray and real-time Polymerase Chain Reaction (PCR) were used to detect gene expression in HNSCC tissues and cell lines. Transwell migration, invasion, wound healing and cell counting kit – 8 (CCK-8) cell assays were used to compare cell migration, invasion and proliferation abilities. Chromatin Immunoprecipitation (ChIP) assays were used to detect SP1 binding to the miR-92b promoter. Western blot was used to detect protein levels. An in vivo tumorigenesis experiment was used to evaluate the effect of SP1 knockdown on tumor growth and protein levels were evaluated by immunohistochemistry. We found that the miR-92b expression level was elevated in HNSCC primary focus tissue compared with adjacent normal tissue, and a higher level of miR-92b was related to a higher clinical stage and worse prognosis of HNSCC patients. MiR-92b and SP1 mutually promoted each expression and cooperatively facilitated the migration, invasion and proliferation of HNSCC cells. A decreased level of SP1/miR-92b resulted in a restraint of in vivo tumor growth. In conclusion, our results suggest that the SP1/miR-92b feedback loop generally promotes HNSCC invasion and metastasis, thus presenting a possible therapeutic target in the treatment of HNSCC patients.