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 theexpression of thyroid transcription factor-1 (TTF-1) and apoptosisand angiogenesis in lung carcinomas.METHODS A 829 microarray of the paraffin tissue chips wasconst...OBJECTIVE To investigate the correlations between theexpression of thyroid transcription factor-1 (TTF-1) and apoptosisand angiogenesis in lung carcinomas.METHODS A 829 microarray of the paraffin tissue chips wasconstructed, which contained 196 lung carcinomas, 10 normallung tissues, and 1 muscular tissue. Terminal deoxynucleotidyltransferase mediated nick end labeling (TUNEL) andimmunohistochemical SP method were used to detect apoptosisand expression of TTF-1 and CD34 in different types of lungcarcinomas. A Leica Q500 MC image analysis system was used tomeasure and calculate TTF-1 positive unit (PU), apoptotic index(AI) and microvessel density (MVD).RESULTS AI of lung small cell carcinoma and large cellcarcinoma were smaller than those of lung adenocarcinoma andsquamous cell carcinoma (P = 0.000). AI of lung carcinomas withlymph node metastases was smaller than that of those without(P = 0.039). AI of lung carcinomas in TNM stage Ⅰ-Ⅳ was smallerthan that in stage Ⅰ (P = 0.008). The PU of the TTF-1 was negativelycorrelated with AI in small cell lung carcinoma (r = -0.752, P =0.000). MVD of lung carcinomas without lymph node metastaseswas smaller than that of those with lymph node metastasis (P= 0.031). MVD of lung carcinomas in TNM stage Ⅰ was smallerthan that in stage Ⅰ-Ⅳ (P = 0.040). The PU of TTF-1 was positivelycorrelated with MVD in lung adenocarcinoma (r = 0.708, P = 0.000).CONCLUSION There is a negative correlation between TTF-1PU and AI in small cell lung carcinoma. TTF-1 PU and AI may becorrelated with each other. There is a positive correlation betweenTTF-1 PU and MVD in lung adenocarcinoma. TTF-1 may inducethe development of lung adenocarcinoma by inducing tumorangiogenesis.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 lymph ...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 signifi cance 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 theexpression of thyroid transcription factor-1 (TTF-1) and apoptosisand angiogenesis in lung carcinomas.METHODS A 829 microarray of the paraffin tissue chips wasconstructed, which contained 196 lung carcinomas, 10 normallung tissues, and 1 muscular tissue. Terminal deoxynucleotidyltransferase mediated nick end labeling (TUNEL) andimmunohistochemical SP method were used to detect apoptosisand expression of TTF-1 and CD34 in different types of lungcarcinomas. A Leica Q500 MC image analysis system was used tomeasure and calculate TTF-1 positive unit (PU), apoptotic index(AI) and microvessel density (MVD).RESULTS AI of lung small cell carcinoma and large cellcarcinoma were smaller than those of lung adenocarcinoma andsquamous cell carcinoma (P = 0.000). AI of lung carcinomas withlymph node metastases was smaller than that of those without(P = 0.039). AI of lung carcinomas in TNM stage Ⅰ-Ⅳ was smallerthan that in stage Ⅰ (P = 0.008). The PU of the TTF-1 was negativelycorrelated with AI in small cell lung carcinoma (r = -0.752, P =0.000). MVD of lung carcinomas without lymph node metastaseswas smaller than that of those with lymph node metastasis (P= 0.031). MVD of lung carcinomas in TNM stage Ⅰ was smallerthan that in stage Ⅰ-Ⅳ (P = 0.040). The PU of TTF-1 was positivelycorrelated with MVD in lung adenocarcinoma (r = 0.708, P = 0.000).CONCLUSION There is a negative correlation between TTF-1PU and AI in small cell lung carcinoma. TTF-1 PU and AI may becorrelated with each other. There is a positive correlation betweenTTF-1 PU and MVD in lung adenocarcinoma. TTF-1 may inducethe development of lung adenocarcinoma by inducing tumorangiogenesis.
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 signifi cance 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.
