Down-regulation of HCP5 inhibits cell proliferation, migration, and invasion through regulating EPHA7 by competitively binding miR-101 in osteosarcoma

Patients with osteosarcoma (OS) usually have poor overall survival because of frequent metastasis. Long non-coding RNAs (lncRNAs) have been reported to be associated with tumorigenesis and metastasis. In this study, we investigated the expression and roles of lncRNA human histocompatibility leukocyte antigen (HLA) complex P5 (HCP5) in OS, aiming to provide a novel molecular mechanism for OS. HCP5 was up-regulated both in OS tissues and cell lines and high expression of HCP5 was associated to low survival in OS patients. Down-regulation of HCP5 inhibited cell proliferation, migration, and invasion, suggesting its carcinogenic role in OS. miR-101 was targeted by HCP5 and its expression was decreased in OS. The inhibitor of miR-101 reversed the impact of HCP5 down-regulation on cell proliferation, apoptosis, and metastasis in OS. Ephrin receptor 7 (EPHA7) was proved to be a target of miR-101 and had ability to recover the effects of miR-101 inhibitor in OS. In conclusion, lncRNA HCP5 knockdown suppressed cell proliferation, migration, and invasion, and induced apoptosis through depleting the expression of EPHA7 by binding to miR-101, providing a potential therapeutic strategy of HCP5 in OS.

Expression of EphA7 and MTDH and clinicopathological significance in the squamous cell cancer of the tongue / 中南大学学报(医学版)

OBJECTIVE@#To determine the expression levels of EphA7 and MTDH and detect their clinicopathological significance in the peritumoral normal tissues and the squamous cell cancer of the tongue.@*METHODS@#Envision immunohistochemistry was used to assay the expression levels of EphA7 and MTDH in the conventional paraffin-embedded sections from specimens of squamous cell cancer (n=45) and peritumoral normal tissues (n=10).@*RESULTS@#The positIVe rates of EphA7 and MTDH were significantly higher in the squamous cell cancer than those in the peritumoral normal tissues ( χ(2)(EphA7)=4.14; χ(2)(MTDH)= 5.25; P < 0.05). The positIVe rates of EphA7 and MTDH expression were significantly lower in the cases of histological grade I-II,clinical stage I-II, and no-metastasis of neck lymph node than those in the histological grade III-IV, clinical stage III-IV, and metastasis of neck lymph node (P <0.05 or P <0.01).@*CONCLUSION@#The expression levels of EphA7 and/or MTDH might have important effect on the carcinogenesis and progression of tongue cancer. Overexpression of EphA7 and/or MTDH might have poor prognosis.

Expression of ephrin-A7 and metadherin and its clinicopathological significances in the benign and malignant lesions of gallbladder / 中华外科杂志

<p><b>OBJECTIVE</b>To study the expression of ephrin-A7 (EphA7) and metadherin (MTDH) and their clinicopathological significances in the benign and malignant lesions of gallbladder.</p><p><b>METHODS</b>EnVisiom immunohistochemical methods was used for determining the expressions of EphA7 and MTDH in routinely paraffin-embedded sections of surgically-resected specimens from 108 cases with gallbladder adenocarcinoma, 15 cases with adenomatous polyp and 35 cases with chronic cholecystitis treated from June 1996 to June 2006. And 46 cases of peritumoral tissues were also harvested as controls (n = 35).</p><p><b>RESULTS</b>The positive expression rates of EphA7 and MTDH were significantly higher in gallbladder adenocarcinoma than those in peritumoral tissues (χ(2)(EphA7) = 12.65, χ(2)(MTDH) = 13.00; P < 0.01), adenomatous polyp (χ(2)(EphA7) = 8.21, χ(2)(MTDH) = 9.39; P < 0.01) and chronic cholecystitis (χ(2)(EphA7) = 21.21, χ(2)(MTDH) = 23.68; P < 0.01); Moderately-or severely-atypical hyperplasia of gallbladder epithelium was found in the benign lesions with positive expression of EphA7 and/or MTDH. The positive rates of EphA7 and MTDH were significantly lower in the cases of well-differentiated adenocarcinoma, maximal diameter of tumor < 2 cm, no-metastasis of lymph node, and tumor with no-invasiveness of regional tissues than those in the poorly-differentiated adenocarcinoma (χ(2)(EphA7) = 12.34, χ(2)(MTDH) = 12.80; P < 0.01), maximal diameter of tumor ≥ 2 cm (χ(2)(EphA7) = 5.22, χ(2)(MTDH) = 5.00; P < 0.05), cases with metastasis of lymph node (χ(2)(EphA7) = 5.15, χ(2)(MTDH) = 5.86; P < 0.05) and cases with invasiveness of regional tissues (χ(2)(EphA7) = 7.06, P < 0.01; χ(2)(MTDH) = 4.13; P < 0.05) in gallbladder adenocarcinoma (P < 0.05). The high consistency was found between the expressive levels of EphA7 and MTDH in gallbladder adenocarcinoma (χ(2) = 13.11, P < 0.01). The univariate Kaplan-Meier analysis showed that the increased expression of EphA7 (P = 0.023) and MTDH (P = 0.034) was negatively associated with the overall survival. The multivariate Cox regression analysis showed that increased expression of EphA7 and/or MTDH (P(EphA2) = 0.023, P(MTDH) = 0.034) was an independent poor-prognostic predictor for gallbladder adenocarcinoma.</p><p><b>CONCLUSIONS</b>The expression of EphA7 and/or MTDH might be closely related to the carcinogenesis, progression, clinical biological behaviors and prognosis of gallbladder adenocarcinoma. The positive expression of EphA7 and/or MTDH may predict bad-prognosis in gallbladder adenocarcinoma.</p>

Expression of EphA7 protein in primary hepatocellular carcinoma and its clinical significance / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the expression and clinical significance of EphA7 protein in primary hepatocellular carcinoma.</p><p><b>METHODS</b>Immunohistochemistry and Western blot were used to detect the expression of EphA7 protein in 40 cases of primary hepatocellular carcinoma, their corresponding adjacent liver tissues and 10 cases of normal liver tissues. The relations with its clinical pathological parameters were analyzed too.</p><p><b>RESULTS</b>Expression of EphA7 protein was mainly located in the cytoplasm and the blood vessels of the septa, which was found in hepatocellular carcinoma tissues, their corresponding adjacent liver tissues and normal liver tissues. Western blot analysis showed that the expression level of EphA7 protein in hepatocellular carcinoma (0.58 +/- 0.26) was greater than that in corresponding adjacent liver tissues (0.40 +/- 0.22, P < 0.05) and normal liver tissues (0.32 +/- 0.16, P < 0.05). But it had no significant difference between corresponding adjacent liver tissues and normal liver tissues (P > 0.05). EphA7 protein expression was correlated with histological differentiation, tumor thrombi in portal vein, lymph node metastasis and high AFP level (P < 0.05).</p><p><b>CONCLUSIONS</b>EphA7 protein expression is significantly correlated with the biological behavior of primary hepatocellular carcinoma. The high expression of EphA7 protein may play an important role in the malignancy transformation, invasion progression and metastasis of primary hepatocellular carcinoma.</p>