BACKGROUND Mesenchymal stem cells(MSCs)exert anti-oncogenic effects via exosomes containing non-coding RNA(ncRNA),which play important roles in tumor biology.Our preliminary study identified the interaction of the ncR...BACKGROUND Mesenchymal stem cells(MSCs)exert anti-oncogenic effects via exosomes containing non-coding RNA(ncRNA),which play important roles in tumor biology.Our preliminary study identified the interaction of the ncRNA hsa_-circ_0000563(circ563)and the circ563-associated miR-148a-3p in exosomes,as miR-148a-3p and its target metal-regulatory transcription factor-1(MTF-1)are implicated in hepatocellular carcinoma(HCC)progression.AIM To identify the clinical significance,functional implications,and mechanisms of circ563 in HCC.METHODS The expression levels of miR-148a-3p and MTF-1 in exosomes derived from MSC and HCC cells were compared,and their effects on HCC cells were assessed.Using a dual-luciferase reporter assay,miR-148a-3p was identified as an associated microRNA of circ563,whose role in HCC regulation was assessed in vitro and in vivo.RESULTS The silencing of circ563 blocked the HCC cell proliferation and invasion and induced apoptosis.Co-culturing of HCC cells with MSC-derived exosomes following circ563 overexpression promoted cell proliferation and metastasis and elicited changes in miR-148a-3p and MTF-1 expression.The tumor-promoting effects of circ563 were partially suppressed by miR-148a-3p overexpression or MTF-1 depletion.Xenograft experiments performed in nude mice confirmed that circ563-enriched exosomes facilitated tumor growth by upregulating the expression of MTF-1.In HCC tissues,circ563 expression was negatively correlated with miR-148a-3p expression but positively correlated with MTF-1 levels.CONCLUSION MSCs may exhibit anti-HCC activity through the exosomal circ563/miR-148a-3p/MTF-1 pathway,while exosomes can transmit circ563 to promote oncogenic behavior by competitively binding to miR-148a-3p to activate MTF-1.展开更多
OBJECTIVE To investigate the correlations between the expression of thyroid transcription factor-1 （TTF-1） and apoptosis and angiogenesis in lung carcinomas. METHODS A 829 microarray of the paraffin tissue chips was...OBJECTIVE To investigate the correlations between the expression of thyroid transcription factor-1 （TTF-1） and apoptosis and angiogenesis in lung carcinomas. METHODS A 829 microarray of the paraffin tissue chips was constructed, which contained 196 lung carcinomas, 10 normal lung tissues, and 1 muscular tissue. Terminal deoxynucleotidyl transferase mediated nick end labeling （TUNEL） and immunohistochemical SP method were used to detect apoptosis and expression of TTF-1 and CD34 in different types of lung carcinomas. A Leica Q500 MC image analysis system was used to measure and calculate TTF-1 positive unit （PU）, apoptotic index （AI） and microvessel density （MVD）. RESULTS AI of lung small cell carcinoma and large cell carcinoma were smaller than those of lung adenocarcinoma and squamous cell carcinoma （P = 0.000）. AI of lung carcinomas with lymph node metastases was smaller than that of those without （P = 0.039）. AI of lung carcinomas in TNM stage I-IV was smaller than that in stage I （P = 0.008）. The PU of the TTF-1 was negatively correlated with AI in small cell lung carcinoma （r = -0.752, P = 0.000）. MVD of lung carcinomas without lymph node metastases was smaller than that of those with lymph node metastasis （P = 0.031）. MVD of lung carcinomas in TNM stage I was smaller than that in stage I-IV （P = 0.040）. The PU of TTF-1 was positively correlated with MVD in lung adenocarcinoma （r = 0.708, P = 0.000）. CONCLUSION There is a negative correlation between TTF-1 PU and AI in small cell lung carcinoma. TTF-1 PU and AI may be correlated with each other. There is a positive correlation between TTF-1 PU and MVD in lung adenocarcinoma. TTF-1 may induce the development of lung adenocarcinoma by inducing tumor angiogenesis.展开更多
OBJECTIVE To compare the expression of the thyroid transcription factor-1 （TTF-1） in human normal adult type Ⅱ alveolar epithelial cells, embryonic pneumocytes and cancer cells of lung carcinoma and metastatic lymp...OBJECTIVE To compare the expression of the thyroid transcription factor-1 （TTF-1） in human normal adult type Ⅱ alveolar epithelial cells, embryonic pneumocytes and cancer cells of lung carcinoma and metastatic lymph nodes using a tissue microarray （TMA） along with paired conventional full sections, and to investigate the reliability of tissue microarrays in detecting protein expression in lung carcinoma. METHODS A lung carcinoma TMA including 765 cores was constructed. TTF-1 protein expression in both TMA and paired conventional full sections were detected by the immunohistochemical SP method using a monoclonal antibody to TTF-1. A PU （Positive Unit） of TTF-1 protein was assessed quantitatively by the Leica Q500MC image analysis system with results from the paired conventional full sections as controls. RESULTS There was no significance between TMA and paired conventional full sections in TTF-1 expression in different nuclei of the lung tissue. CONCLUSION TTF-1 protein expression in lung carcinoma detected by TMA was highly concordant with that of paired full sections. TMA is a reliable method in detecting protein expression.展开更多
基金the National Natural Science Foundation of China,No.81972606 and 82271774.
文摘BACKGROUND Mesenchymal stem cells(MSCs)exert anti-oncogenic effects via exosomes containing non-coding RNA(ncRNA),which play important roles in tumor biology.Our preliminary study identified the interaction of the ncRNA hsa_-circ_0000563(circ563)and the circ563-associated miR-148a-3p in exosomes,as miR-148a-3p and its target metal-regulatory transcription factor-1(MTF-1)are implicated in hepatocellular carcinoma(HCC)progression.AIM To identify the clinical significance,functional implications,and mechanisms of circ563 in HCC.METHODS The expression levels of miR-148a-3p and MTF-1 in exosomes derived from MSC and HCC cells were compared,and their effects on HCC cells were assessed.Using a dual-luciferase reporter assay,miR-148a-3p was identified as an associated microRNA of circ563,whose role in HCC regulation was assessed in vitro and in vivo.RESULTS The silencing of circ563 blocked the HCC cell proliferation and invasion and induced apoptosis.Co-culturing of HCC cells with MSC-derived exosomes following circ563 overexpression promoted cell proliferation and metastasis and elicited changes in miR-148a-3p and MTF-1 expression.The tumor-promoting effects of circ563 were partially suppressed by miR-148a-3p overexpression or MTF-1 depletion.Xenograft experiments performed in nude mice confirmed that circ563-enriched exosomes facilitated tumor growth by upregulating the expression of MTF-1.In HCC tissues,circ563 expression was negatively correlated with miR-148a-3p expression but positively correlated with MTF-1 levels.CONCLUSION MSCs may exhibit anti-HCC activity through the exosomal circ563/miR-148a-3p/MTF-1 pathway,while exosomes can transmit circ563 to promote oncogenic behavior by competitively binding to miR-148a-3p to activate MTF-1.
文摘OBJECTIVE To investigate the correlations between the expression of thyroid transcription factor-1 （TTF-1） and apoptosis and angiogenesis in lung carcinomas. METHODS A 829 microarray of the paraffin tissue chips was constructed, which contained 196 lung carcinomas, 10 normal lung tissues, and 1 muscular tissue. Terminal deoxynucleotidyl transferase mediated nick end labeling （TUNEL） and immunohistochemical SP method were used to detect apoptosis and expression of TTF-1 and CD34 in different types of lung carcinomas. A Leica Q500 MC image analysis system was used to measure and calculate TTF-1 positive unit （PU）, apoptotic index （AI） and microvessel density （MVD）. RESULTS AI of lung small cell carcinoma and large cell carcinoma were smaller than those of lung adenocarcinoma and squamous cell carcinoma （P = 0.000）. AI of lung carcinomas with lymph node metastases was smaller than that of those without （P = 0.039）. AI of lung carcinomas in TNM stage I-IV was smaller than that in stage I （P = 0.008）. The PU of the TTF-1 was negatively correlated with AI in small cell lung carcinoma （r = -0.752, P = 0.000）. MVD of lung carcinomas without lymph node metastases was smaller than that of those with lymph node metastasis （P = 0.031）. MVD of lung carcinomas in TNM stage I was smaller than that in stage I-IV （P = 0.040）. The PU of TTF-1 was positively correlated with MVD in lung adenocarcinoma （r = 0.708, P = 0.000）. CONCLUSION There is a negative correlation between TTF-1 PU and AI in small cell lung carcinoma. TTF-1 PU and AI may be correlated with each other. There is a positive correlation between TTF-1 PU and MVD in lung adenocarcinoma. TTF-1 may induce the development of lung adenocarcinoma by inducing tumor angiogenesis.
基金the National Natural Sciences Foundation of China (No. 30271462)the science and technology planning project of Guangdong Province (No. 2KM04501S)the principal science and technology project of Guangzhou City (No. 2003Z2-E0061, E0062).
文摘OBJECTIVE To compare the expression of the thyroid transcription factor-1 （TTF-1） in human normal adult type Ⅱ alveolar epithelial cells, embryonic pneumocytes and cancer cells of lung carcinoma and metastatic lymph nodes using a tissue microarray （TMA） along with paired conventional full sections, and to investigate the reliability of tissue microarrays in detecting protein expression in lung carcinoma. METHODS A lung carcinoma TMA including 765 cores was constructed. TTF-1 protein expression in both TMA and paired conventional full sections were detected by the immunohistochemical SP method using a monoclonal antibody to TTF-1. A PU （Positive Unit） of TTF-1 protein was assessed quantitatively by the Leica Q500MC image analysis system with results from the paired conventional full sections as controls. RESULTS There was no significance between TMA and paired conventional full sections in TTF-1 expression in different nuclei of the lung tissue. CONCLUSION TTF-1 protein expression in lung carcinoma detected by TMA was highly concordant with that of paired full sections. TMA is a reliable method in detecting protein expression.
