MAC30 Expression Research Articles

MAC30 Knockdown Inhibits Proliferation and Enhance Apoptosis of Gastric Cancer by Suppressing Wnt/β-Cateninsignaling Pathway.

Gastric cancer is one of the most frequently diagnosed cancer and poses a serious threat to health system in the world. Upregulation of meningioma-associated protein (MAC30) has been found in many solid tumors and can regulate the proliferation, differentiation, and apoptosis of different tumor cells. Quantitative polymerase chain reaction (qPCR) was used to detect the expression of MAC30 in 68 patients with gastric cancer and their adjacent tissues. Lentiviral vector pGCSIL-shMAC30-GFP of the RNA interference (RNAi) of the MAC30 gene was transfected into gastric cancer BGC-823 cell line and the expression of lentivirus label protein GFP was observed via fluorescence microscope, while cell proliferation and apoptosis were determined with flow cytometry and MTT assay, respectively. Also, related protein expressions on Wnt/β-catenin signaling pathway were analyzed by Western blot method. The expression of MAC30 was abnormally elevated in gastric cancer tissues, while interfering of its expression could significantly inhibit the proliferation of gastric cancer BGC-823 cell line. However, the promotion of apoptosis by mitochondrial pathway was mediated by Bax/Bcl-2 upregulation. Present work showed the effect of downregulated MAC30 expression on proliferation and apoptosis of gastric cancer cell through Wnt/β-catenin signaling pathway. Thus, this investigation provides an experimental basis for future development of chemotherapeutic agent on gastric cancer.

MAC30 knockdown involved in the activation of the Hippo signaling pathway in breast cancer cells.

Down-regulation of the meningioma-associated protein (MAC30) gene has been found in many solid cancers. This study was carried out to determine the roles and the mechanisms of MAC30 in breast cancer. We used our own data and a public database to analyze the MAC30 mRNA and protein levels in breast cancer tissues. In addition, we established MAC30 knockdown breast cancer cells using MAC30 siRNA. The roles of MAC30 were detected by using the Soft agar assay, Annexin-V-FITC/PI double staining and the Transwell assay. Western blotting was used to analyze the potential mechanism(s) of MAC30 in these cells. We found that MAC30 mRNA and protein were higher in the cancer tissues compared to the matched normal tissues. MAC30 expression was associated with tumor size, tumor differentiation and estrogen receptor (ER) status. Overall survival rate of the patients with low MAC30 expression was obviously higher than the ones with high expression. The apoptotic ratio was lower in MDA-MB-231 and MDA-MB-157 cells with MAC30 expression. By Western blot analysis, we found that increased levels of phosphorylated YAP1, MST1 and LATS1 after MAC30 siRNA transfection in these two cells. In summary, we demonstrate that MAC30 knockdown is involved in the activation of the Hippo signaling pathway.

Pleural MAC30 as a prognostic marker in NSCLC with malignant pleural effusion.

Over-expressed meningioma-associate protein (MAC30) in tissues was associated with malignant tumor differentiation, metastasis and poor prognosis. However, the attention of MAC30 in pleural effusion from lung tumor is insufficient. Our retrospective study was prepared to explore the clinical values on diagnosis and prognosis of MAC30 from malignant pleural effusion (MPE) in non-small cell lung cancer (NSCLC). Levels of MAC30 were confirmed in MPE from 48 NSCLC patients and in benign pleural effusion (BPE) from 45 controls via enzyme-linked immunosorbent assay (ELISA). The association of MAC30 in MPE with clinical significance was further determined. We found that the levels of MAC30 in MPE were obviously higher than those in BPE (p < 0.05). Moreover, with a cutoff point (17.5 ng/ml), we confirmed the sensitivity and specificity of MAC30 for MPE were 82.7% and 85.3% using ROC curve analysis. Indeed, longer overall survival (OS) was present in NSCLC patients with low MAC30 expression in MPE. Multivariate analysis explicated that elevated MAC30 in MPE was an independent prognostic factor for shorter OS of NSCLC. Our data suggests that MAC30 in pleural effusion could be a potential prognostic marker in NSCLC with MPE.

The Prognostic Effect of MAC30 Expression on Patients With Non-Small Cell Lung Cancer Receiving Adjuvant Chemotherapy.

The purpose of this study was to examine the MAC30 expression in non-small cell lung cancer and to evaluate its prognostic value on therapeutic response in patients with non-small cell lung cancer receiving postoperative chemotherapy. Among a total of 218 retrospective Chinese patients with non-small cell lung cancer, 164 patients receiving adjuvant chemotherapy were enrolled in this study. Real-time polymerase chain reaction was performed to confirm the expression of MAC30 messenger RNA in 32 cases of non-small cell lung cancer tumors with the corresponding nontumor lung tissues. The MAC30 protein expression in all specimens was analyzed by immunohistochemical staining. Moreover, we assessed the correlation of MAC30 expression with clinicopathological features, therapeutic response, and survival of patients. Here, we observed the increased expression of MAC30 messenger RNA in patients with non-small cell lung cancer compared to those in control samples. The overexpression of MAC30 was strongly associated with poor tumor differentiation, high tumor-node-metastasis stage, and lymph node metastasis. In addition, we observed that patients with increased MAC30 expression showed gloomy overall survival and disease-free survival. A multivariate analysis explicated that higher MAC30 expression was a valuable independent prognostic factor of poorer tumor differentiation, shorter overall survival, and disease-free survival in patients receiving chemotherapy. MAC30 could be a useful biomarker of tumor differentiation and outcome of patients with non-small cell lung cancer. Overexpression of MAC30 predicts a worse tumor differentiated stage and prognosis in patients with non-small cell lung cancer receiving adjuvant chemotherapy.

Overexpression of MAC30 is Resistant to Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer.

Adjuvant platinum-based chemotherapy has developed its stability as the first-line treatment in advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the prognostic value of meningioma-associated protein (MAC30) on adjuvant platinum-based chemotherapeutic response and survival in patients with NSCLC. A total of 174 retrospective stage III B to IV Chinese patients with NSCLC were enrolled in the study. Among all cases, 85 patients were given platinum-based chemotherapy and another 89 patients received molecularly targeted therapy. The expression of MAC30 in tumor samples was confirmed via immunohistochemical staining to correlate with the therapeutic response and survival of patients. Patients having NSCLC with MAC30 overexpression showed a poorer response to platinum-based chemotherapy, while there was no prognostic value of MAC30 expression on molecularly targeted therapy. Further, patients receiving platinum-based chemotherapy with enhanced MAC30 expression exhibited shorter survival. A multivariate analysis exhibited that increased MAC30 expression was an independent prognostic factor for overall survival in patients having NSCLC with platinum-based chemotherapy. In conclusion, patients having NSCLC with higher MAC30 expression resisted to platinum-based chemotherapy and exhibited worse survival.

Down-Regulated MAC30 Expression Inhibits Proliferation and Mobility of Human Gastric Cancer Cells

Background: Gastric cancer is one of the most common cancers in the world. MAC30/Transmembrane protein 97 (TMEM97) is aberrantly up-regulated in many human carcinoma cells. However, the function of MAC30 in gastric carcinoma cells is not studied. Material and Methods: To investigate the function of MAC30 in gastric carcinoma, we used RNA silencing technology to knock down the expression of MAC30 in gastric cancer cells BGC-823 and AGS. Real-time quantitative PCR and Western blot were used to analyze the mRNA level and the related protein expression. The localization of MAC30 and lamellipodia was observed by immunofluorescence. The biological phenotypes of gastric cells were examined by cell proliferation assay, cell cycle analysis, apoptosis assay, cell migration and invasion assay. Results: We found that down-regulation of MAC30 expression efficiently inhibited the proliferation of gastric cancer cells. Furthermore, the mobility of gastric cancer cells was also inhibited by down-regulation of MAC30. Moreover, we found that MAC30 knockdown inhibited AKT phosphorylation and reduced the expression of cyclinB1 and WAVE2. Conclusion: To our knowledge, this is the first report investigating the effect of MAC30 on growth, cell cycle, migration, and invasion in gastric carcinoma cells via suppressing AKT signaling pathway. MAC30 may be a potential therapeutic target for treatment of gastric carcinoma.

Elevated expression of MAC30 predicts lymph node metastasis and unfavorable prognosis in patients with epithelial ovarian cancer

Meningioma-associated protein (MAC30), first described to be overexpressed in meningiomas, exhibits altered expression in certain human tumors. The definite role of MAC30 is not clear now, and few studies have documented the value of MAC30 in epithelial ovarian cancer (EOC). The aim of this study was to investigate the expression of MAC30 in EOC and to evaluate its clinical significance in patients with EOC. A total of 266 patients with EOC who undergone complete cytoreductive surgery from November 2003 to September 2006 were eligible for this study. The expression of MAC30 in epithelial ovarian tumor tissues was examined immunohistochemically. High expression of MAC30 was observed in 66.17 % of EOC. The high MAC30 expression group had more advanced stages, poorer histological grade, lymph node metastasis, and recurrence than those with low MAC30 expression. Moreover, the presence of lymph node metastasis was significantly associated with MAC30 expression (OR 2.888, 95 % CI 1.428-5.838, P = 0.003). In addition, it was also shown that high MAC30 expression significantly correlated with poorer overall survival and progression-free survival (both P < 0.001). Multivariate Cox regression analysis revealed that MAC30 expression status was an independent prognostic factor for both overall survival and progression-free survival (P = 0.001 and P = 0.002, respectively) of patients with EOC. Our study provides evidence that patients with expression of MAC30 in EOC have high malignant potential, and MAC30 may serve as a new molecular marker to predict the lymph node metastasis and prognosis of patients with EOC in the clinic.

Overexpression of MAC30 is associated with poor clinical outcome in human non-small-cell lung cancer

The aim of this study was to detect MAC30 expression in human non-small cell lung cancer (NSCLC) and to analyze its association with prognosis of NSCLC patients. Quantitative real-time RT-PCR was performed to examine the expression of MAC30 mRNA in 20 cases of NSCLC and corresponding non-tumor tissue samples. Immunohistochemistry was performed to detect the expression of MAC30 in 95 NSCLC tissues. We found that the expression levels of MAC30 mRNA in NSCLC tissues were significantly higher than those in corresponding non-tumor tissues. High-level MAC30 expression was correlated with poor tumor differentiation, TNM stage, and lymph node metastasis. Patients with high expression levels of MAC30 showed lower overall survival rate than those with low expression levels. Multivariate analysis showed that high MAC30 protein expression was an independent prognostic factor for NSCLC patients. Our study suggests that over-expression of MAC30 may play an important role in the progression of NSCLC and MAC30 expression may offer a valuable marker for predicting the outcome of patients with NSCLC.

Expression of MAC30 protein is related to survival and clinicopathological variables in breast cancer

MAC30 is a protein with unknown function that is differentially expressed in certain malignancies. The aims of this study were to evaluate the relationship between MAC30 expression and clinicopathologic features while investigate the prognostic value of MAC30 expression in breast cancer. Immunohistochemistry was used to examine MAC30 expression in 243 breast cancer tissues, meanwhile in 59 matched adjacent noncancerous tissues and 46 benign breast tumor tissues as controls. The correlation of MAC30 expression with clinicopathological parameters was assessed using χ(2) analysis. The Kaplan-Meier method and Cox proportional hazards model were used to predict factors with a significant independent prognostic value. MAC30 was overexpressed in breast cancer compared with matched adjacent noncancerous tissues and benign breast tumor (both P < 0.001). Moreover, MAC30 expression was correlated with tumor size, TNM stage, lymph node metastasis, and recurrence. Furthermore, it was shown that patients with high MAC30 expression had significantly poorer overall survival (OS) and disease-free survival (DFS; P = 0.002 and P = 0.007, respectively). Multivariate Cox regression analysis revealed that high MAC30 expression was an independent prognostic factor for both OS and DFS (P = 0.018 and P = 0.044, respectively). Overexpression of MAC30 was associated with tumor progression, recurrence, and poor survival in breast cancer. Testing expression of MAC30 will be helpful for predicting prognosis in breast cancer.

Overexpression of MAC30 in the Cytoplasm of Oral Squamous Cell Carcinoma Predicts Nodal Metastasis and Poor Differentiation

Background: Expression of the meningioma-associated protein (MAC30) was increased in several types of tumors, including esophageal, gastric and colon tumors, compared to normal tissue. MAC30 expression levels gradually increased from normal colorectal mucosa to primary colorectal cancer and colorectal cancer spreading to the lymph nodes. MAC30 expression was related to survival in patients with colorectal cancer. However, there is no study on MAC30 in oral squamous cell carcinoma (OSCC). Methods: Therefore, MAC30 expression in OSCC was investigated and possible associations of MAC30 expression with clinicopathological variables in OSCC have been analyzed. MAC30 expression was immunohistochemically examined in 20 normal oral mucosa and 43 OSCC specimens. Results: Expression levels of MAC30 in the cytoplasm markedly increased from normal oral epithelial cells to primary OSCC. Strong cytoplasmic staining was significantly higher in primary OSCC compared to normal oral mucosa samples (51 vs. 20%, p = 0.019). Furthermore, MAC30 expression levels in primary tumors of patients with lymph node metastasis exceeded levels in those without metastasis (65 vs. 35%, p = 0.048), and MAC30 expression in poorly differentiated tumors was higher than in well-differentiated ones (90 vs. 39%, p = 0.005). Conclusion: Overexpression of MAC30 in the cytoplasm of OSCC may predict nodal metastasis and poor differentiation.

Expression of MAC30 in Rectal Cancers with or without Preoperative Radiotherapy

Objective: Meningioma-associated protein (MAC30) is overexpressed in several types of cancers, but its therapeutic implication in the patients has not been studied. We examined the relationship of MAC30 with clinicopathological and biological factors in rectal cancer patients with or without radiotherapy (RT). Methods: MAC30 was immunohistochemically examined in 75 distant and 91 adjacent normal mucosa specimens, 132 primary tumours and 39 lymph node metastases from rectal cancer patients participating in a clinical trial of preoperative RT. Results: In the RT group, MAC30 was or tended to be positively correlated with infiltrated growth pattern (p = 0.02), PRL (phosphatase of regenerating liver, p = 0.01) and Ki-67 expression (p = 0.06). MAC30 at the invasive margin of the metastasis was related to poor survival (p = 0.02) in the whole group of patients. MAC30 in primary tumours was not related to recurrence and survival in the non-RT or RT group. Conclusions:MAC30 expression in metastasis was an indicator for poor survival. After RT, MAC30 seemed to be more related to aggressive morphological and biological factors; however, we did not find direct evidence that MAC30 expression was related to the outcome of patients with or without RT.

Expression of MAC30 protein is related to survival and biological variables in primary and metastatic colorectal cancers

MAC30 is highly expressed in several types of tumors including colorectal cancers, however, its clinicopathological and biological significance in colorectal cancers is currently not known. The aim of our study was to investigate MAC30 expression in distant normal mucosa, adjacent normal mucosa, primary tumors and metastases of colorectal cancer, and to determine the relationship between MAC30 expression and clinicopathological and biological variables. MAC30 expression was immunohistochemically examined in distant normal mucosa (n = 54), adjacent normal mucosa (n = 123), primary tumors (n = 217) and lymph node metastases (n = 56) from colorectal cancer patients. MAC30 cytoplasmic expression was increased from distant normal mucosa to primary tumor and to metastasis (p < 0.0001-0.04). Furthermore, 40% primary and 37% metastatic tumors showed stronger cytoplasmic expression of MAC30 at the tumor invasive margins compared to inner tumor areas. Strong cytoplasmic expression of MAC30 in the metastasis was related to a poor prognosis (p = 0.04). MAC30 cytoplasmic expression was positively related to expression of proliferating cell nuclear antigen (p = 0.04), p53 (p = 0.04), nucleoporin 88 (p = 0.001), legumain (p = 0.004) and particularly interesting new cysteine-histidine rich protein (p = 0.004). However, MAC30 expression in the nucleus and stroma did not have any clinicopathological and biological significance (p > 0.05). In conclusion, MAC30 protein may play a role in development of colorectal cancer, and can be considered as a prognostic factor.

Expression analysis of MAC30 in human pancreatic cancer and tumors of the gastrointestinal tract.

Meningioma-associated protein, MAC30, is a protein with unknown function and cellular localization that is differentially expressed in certain malignancies. In the present study, the expression of MAC30 in a variety of normal and cancerous human gastrointestinal tissues, with special emphasis on pancreatic tissues was analyzed. Quantitative RT-PCR was utilized to compare MAC30 expression levels. In situ hybridization and immunohistochemistry were carried out to localize MAC30 mRNA and protein expression in normal and cancerous tissue samples of the esophagus, stomach, colon and pancreas. Furthermore, the effects of TGF-beta on the transcription of MAC30 mRNA were examined in pancreatic cancer cells. MAC30 mRNA was expressed in a wide variety of normal human tissues, being most abundant in testicular and gastric tissue samples. MAC30 mRNA levels were significantly increased in breast and colon cancer, but significantly decreased in pancreatic and renal cancer. TGF-beta down-regulated MAC30 mRNA levels in certain pancreatic cancer cells. MAC30 protein was localized in normal pancreatic tissues, mainly in acinar and islet cells, and in normal colon, gastric and esophageal tissues especially in the mucosal cells. MAC30 was strongly present in tubular complexes in pancreatic cancer tissues but weak to absent in pancreatic cancer cells of primary tumors and metastases. In contrast, esophageal, gastric and colon tumors displayed strong MAC30 immunoreactivity in the cancer cells. In conclusion, MAC30 is expressed in various normal and diseased human tissues. MAC30 up-regulation in certain tumors and down-regulation in others suggests that this protein plays a distinct role in human malignancies.