Expression Level Of Mucin 1 Research Articles

Mucin 1 promotes salivary gland cancer cell proliferation and metastasis by regulating the epidermal growth factor receptor signaling pathway

Background/purposeSalivary gland cancer (SGC) is the common malignant tumor of the head and neck region with poor prognosis. Mucin 1 (MUC1) has been reported to be associated with the development of cancer. However, whether MUC1 contributed to the progression of SGC remains to be explored. Materials and methodsImmunohistochemical analysis was used to explore the expression levels of MUC1 in SGC tissues. Cell proliferation, colony formation, wound healing, transwell, and xenograft assays were performed to examine the effects of MUC1 on SGC in vitro and in vivo. ResultsWe found that the expression level of MUC1 was significantly upregulated in SGC tissues, and the expression level of MUC1 was significantly correlated with lymph node metastasis and TNM stage of SGC. Further exploration demonstrated that MUC1 knockdown drastically inhibited, while its overexpression promoted, cell growth, colony formation, migration, and invasion abilities of SGC cells in vitro. MUC1 knockdown significantly inhibited tumor growth in vivo, and vice versa. More importantly, we found that MUC1 promotes malignant phenotypes of SGC cells by regulating the epidermal growth factor receptor (EGFR) signaling pathway. ConclusionOur results revealed that MUC1 promotes the development of SGC by mediating the EGFR signaling pathway, which highlights the potential therapeutic target of MUC1/ EGFR in SGC.

Expression of MUC1 in different tumours and its clinical significance (Review).

Mucin 1 (MUC1) was the first discovered transmembrane protein of the mucin family; it normally covers epithelial cells of the mucous membrane, providing lubrication and protection. However, aberrant expression of MUC1 is involved in cancer development, invasion and metastasis. It has been reported that MUC1 upregulation is highly associated with the progression of different epithelial cancer types, such as lung, liver, pancreatic and breast cancer. Therefore, MUC1 can be used as a specific marker and a target for immunotherapy in clinical applications, and the detection of MUC1 expression levels can be used to diagnose the occurrence, metastasis, prognosis and recurrence of cancer. The present review summarizes the abnormal expression of MUC1 in different tumours and discusses its clinical significance, thereby highlighting the potential diagnostic and therapeutic significance of MUC1 in cancer.

Prognostic impact of MUC1 and potential regulatory miR-145 and miR-21 expression in salivary mucoepidermoid carcinoma.

Salivary gland mucoepidermoid carcinoma (MEC) poses a considerable risk of locoregional and distant metastasis after conventional treatments. There is an evident need for specifying prognostic biomarkers to identify patients who are in need of more intensive and prolonged follow-ups. This study aimed to assess the mucin 1 (MUC1) expression level and its potential regulatory microRNAs in salivary gland MEC and their prognostic potentials. The expression of MUC1 in salivary gland MEC tissues was assessed in 47 samples using immunohistochemistry. Related microRNA (miR-145 and miR-21) were evaluated using quantitative Reverse Transcription PCR. The associations between MUC1 and microRNAs expressions and clinicopathological parameters were investigated. MUC1 expression levels positively correlated with histologic grade (p < 0.001), clinical stage (p = 0.04), risk of nodal metastasis (p = 0.02), as well as the likelihood of opting for radical treatment (p = 0.01). Increased expression of miR-21 (p < 0.001) and decreased expression of miR-145 (p < 0.001) were observed in MECs compared to normal salivary gland tissue. MiR-145 negatively (p = 0.01) and miR-21 positively (p = 0.01) correlated with MUC1 overexpression. Based on the univariate cox proportional hazard model, histologic grade and MUC1 expression level were significantly associated with disease-free, cancer-specific, and overall survival. However, the multivariable cox proportional hazard model indicated tumor grade as the only prognostic factor associated with disease-free survival. Our results support the tumor suppressor role of miR-145 and the oncogenic role of miR-21 in salivary gland MEC. Also, MUC1 and miR-145 overexpression, as well as miR-21 suppression, show promising association with histologic tumor grade and clinical stage.

Transmembrane Mucin 1 Blocks Fluorescein Ingress to Corneal Epithelium.

PurposeTo determine the role of transmembrane mucins in blocking fluorescein ingress to the corneal epithelium and its deficiency in contributing to corneal fluorescein punctate staining.MethodsA dry eye model was established by extirpating lacrimal and Harderian glands in rabbits to correlate the expression of mucins with fluorescein-stained areas on the corneal button using immunofluorescence. Expression of transmembrane mucins was promoted in human corneal epithelial cells (HCECs) by culturing with the mucin-promoting medium (MPM) or diquafosol treatment. Conversely, the expression of mucins was downregulated by knockdown with short hairpin RNA. The role of mucin1 extracellular domain in fluorescein ingress was further verified by overexpression of N-terminally truncated mucin1 in HCECs.ResultsIn the rabbit dry eye model, the expression level of mucin1 was significantly decreased in superficial corneal epithelial cells where fluorescein punctate staining was observed. Upregulation of mucin1 and mucin16 in HCECs promoted by MPM or by diquafosol treatment impeded intracellular fluorescein ingress. Downregulation of mucin1 and mucin16 enhanced fluorescence ingress in HCECs after fluorescein staining. Overexpression of truncated mucin1 did not alter the fluorescein intensity of fluorescein-stained HCECs, supporting the notion that the ability of mucin1 to block fluorescein ingress was primarily mediated by its extracellular domain. Minimal inherent expression of mucin16 in the rabbit cornea limited the validation of its role in blocking fluorescein ingress in vivo.ConclusionTransmembrane mucin1 blocks fluorescein ingress in the corneal epithelium, explaining how fluorescein staining is positive when the level of transmembrane mucins is disturbed in dry eyes.

Expression of Mucin1 in saliva in oral squamous cell carcinoma and oral potentially malignant disorders (case control study).

Overexpression of mucin1 is found in head and neck squamous cell carcinoma tissues compared with adjacent non-neoplastic tissues and higher levels are associated with metastasis and invasion. The expression level of mucin1 in saliva of normal individuals, oral potentially malignant disorders and oral squamous cell carcinoma patients and its correlation to clinical and histological variables was evaluated. Forty oral potentially malignant disorders, 40 oral squamous cell carcinoma subjects, and 20 age matched-controls were included. Stimulated salivary samples were collected from all participants, and mucin1 expression was measured by real-time PCR. Mucin1 expression in saliva was significantly elevated in oral potentially malignant disorders when compared with controls. Similarly, mucin1 expression was significantly elevated in oral squamous cell carcinoma group when compared with oral potentially malignant disorders and controls. Mucin1 expression in OSCC patient showed significant positive correlations with T classification and distant Metastasis. Mucin1 expression in oral potentially malignant disorders patients showed significant positive correlations with degree of dysplasia. The expression level of mucin1 in saliva might be a potential biomarker for diagnosing oral potentially malignant disorders and oral squamous cell carcinoma.

Mucin1 expression and gustatory function in postmenopausal females: A case-control observational study.

Investigating possible relationship between Mucin1 expression levels in saliva, gustatory function, and taste perception in postmenopausal females. Using whole mouth taste test, twenty-five post-menopausal females (51.35 ± 5.22 years) and twenty-five premenopausal females (39.65 ± 6.46 years) were prospectively evaluated for gustatory function. The expression of mucin1 was investigated; RNA was isolated from stimulated whole saliva samples and real-time PCR was used to determine mucin1 mRNA levels relative to bactin and GAPDH mRNA levels. Significant difference was observed between postmenopausal and premenopausal women regarding intensity judgments of all tastants. The difference was more evident for sucrose taste perception (p<0.00001). Mucin1 expression levels were significantly decreased in postmenopausal females compared with premenopausal ones (p<0.00001). Mucin1 expression level had significant negative correlation with the salt taste sensitivity but did not correlate significantly with intensity judgments of the other tastants. Postmenopausal women have a reduced gustatory function, especially sucrose. Mucin1 expression was significantly decreased in postmenopausal females and had a significant negative correlation with the salt taste sensitivity. However, no correlation was found between mucin1 expression level and taste sensitivity of other tastants. Key words:Gustatory function, MUC1, taste, postmenopausal.

Overexpression of Mucin 1 Suppresses the Therapeutical Efficacy of Disulfiram against Canine Mammary Tumor.

Simple SummaryCanine mammary tumor is one of the most prevalent canine tumor types in China. Clinical studies showed that the high expression of mucin 1 (MUC1) protein is significantly associated with the malignancy and poor prognosis of canine mammary tumor. Therefore, it is worthwhile to investigate the expression of mucin 1 in developing treatments against canine mammary tumors. In the present study, it is demonstrated that disulfiram, an approved medication in treating human alcoholism, also has inhibitory effects on the growth of canine mammary tumor cells both in vitro and in vivo. With the overexpression of MUC1, the inhibitory effects of disulfiram decrease accordingly. Moreover, disulfiram is shown to inhibit phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (Akt) signaling transduction, which is attenuated by MUC1 overexpression. Overall, these results indicate that the expression level of MUC1 is detrimental to determining the anti-tumor activity of disulfiram. Further consideration should be given when treating the canine mammary tumor with disulfiram or other PI3K/Akt inhibitors.Mucin 1 (MUC1), a transmembrane protein, is closely associated with the malignancy and metastasis of canine mammary tumors; however, the role of overexpressed MUC1 in the development of cancer cells and response to drug treatment remains unclear. To address this question, we developed a new canine mammary tumor cell line, CIPp-MUC1, with an elevated expression level of MUC1. In vitro studies showed that CIPp-MUC1 cells are superior in proliferation and migration than wild-type control, which was associated with the upregulation of PI3K, p-Akt, mTOR, Bcl-2. In addition, overexpression of MUC1 in CIPp-MUC1 cells inhibited the suppressing activity of disulfiram on the growth and metastasis of tumor cells, as well as inhibiting the pro-apoptotic effect of disulfiram. In vivo studies, on the other side, showed more rapid tumor growth and stronger resistance to disulfiram treatment in CIPp-MUC1 xenograft mice than in wild-type control. In conclusion, our study demonstrated the importance of MUC1 in affecting the therapeutical efficiency of disulfiram against canine mammary tumors, indicating that the expression level of MUC1 should be considered for clinical use of disulfiram or other drugs targeting PI3K/Akt pathway.

Inhibition of MUC1 exerts cell-cycle arrest and telomerase suppression in glioblastoma cells

Mucin 1 (MUC1) is a transmembrane glycoprotein involved in tumorigenesis of diverse cancers. However, the role of MUC1 in glioblastoma (GBM) has not yet been fully explored. In this study, the anticancer mechanism of MUC1 suppression in GBM was investigated. The expression level of MUC1 was analyzed in human glioma and paired normal brain tissues. MUC1 was overexpressed in GBM and was negatively associated with overall survival. Moreover, we silenced MUC1 to investigate its effect in GBM cell lines and found that knockdown of MUC1 inhibited cell proliferation and resulted in cell cycle arrest at G1 phase. MUC1 silencing decreased the phosphorylation of RB1 and increased the expression of CDKN1B. Gene set enrichment analysis showed that a series of genes related to cell cycle, telomere maintenance and transforming growth factor Beta (TGF-β) signaling in epithelial mesenchymal transition (EMT) were influenced by MUC1 knockdown. Notably, the reduced TERT expression levels combined with impaired telomerase activity and the switching of telomere maintenance mechanism to alternative lengthening of telomeres (ALT) were observed after MUC1 knockdown. Our results support the role of MUC1 in oncological process in GBM which can be developed as a therapeutic target for cell cycle control and telomere maintenance mechanism.

Integrated Bioinformatics analysis and clinical validation reveals that high expression of mucin 1 in intrahepatic cholangiocarcinoma predicts recurrence after curative resection.

Intrahepatic cholangiocarcinoma (ICC) is a cancer type with high malignancy and a current lack of biomarkers to predict recurrence. In the present study, to identify potential biomarkers, five ICC datasets from the Gene Expression Omnibus database were analyzed to construct initial datasets by using a robust rank aggregation approach. A total of 19 upregulated genes were identified in the initial datasets. The genes identified were then further analysed using data from The Cancer Genome Atlas. Only mucin 1 (MUC1) exhibited significance regarding differential expression and survival prediction. Finally, the expression levels of MUC1 were assessed using reverse transcription-quantitative PCR in 61 pairs of ICC tumor and matched non-cancerous samples. The expression of MUC1 was significantly elevated in ICC tissues compared with that in matched non-cancerous counterparts (P=0.001). Patients with high MUC1 expression levels had significantly shorter overall survival (OS, P=0.009) and recurrence-free survival (RFS, P=0.012). MUC1 was identified as an independent prognostic factor for OS [hazard ratio (HR)=2.364, 95%CI: 1.214-4.485; P=0.023] and RFS (HR=2.552 95%CI: 1.294-5.032; P=0.007) in the multivariate analysis. Using receiver operating characteristic analysis, a co-index including MUC1 had a high accuracy for predicting survival [MUC1 combined with serum levels of CEA and cancer antigen 19-9, and lymph node metastasis, area under curve (AUC)=0.746, 95%CI: 0.620-0.872] and recurrence (MUC1 combined with bile duct invasion and lymph node metastasis, AUC=0.729, 95%CI: 0.605-854). In conclusion, MUC1 is highly expressed in ICC tissue and is a potential prognostic biomarker and therapeutic target for ICC.

Overexpression of MUC1 predicts poor prognosis in patients with breast cancer

Breast cancer is the most commonly diagnosed cancer in females; thus, there is an urgent requirement to identify precise biomarkers for the diagnosis and treatment of the disease. Mucin 1 (MUC1) is a glycoprotein that has been demonstrated to be involved in the metastasis and invasion of multiple tumor types. Bioinformatics analyses were conducted to indicate the prognostic value of MUC1 in breast cancer. Additionally, the expression level of MUC1 was assessed using Oncomine analysis. Furthermore, PrognoScan was used to analyze the prognostic value of MUC1 in breast cancer. Mutations of MUC1 were analyzed by the Catalogue of Somatic Mutations in Cancer and cBioPortal databases. In addition, University of California, Santa Cruz (UCSC) was used to examine the methylation status of MUC1. Co-expression of MUC1 mRNA was detected with the cBioPortal, UCSC and Breast Cancer Gene-Expression Miner v4.0 datasets. The results demonstrated that MCU1 is frequently overexpressed in breast cancer and is negatively associated with CpG sites. Furthermore, pooled data indicated that abnormally high expression of MUC1 indicates poor prognosis. Additionally, upregulation of MUC1 expression is associated with estrogen receptor- and progesterone receptor-positive disease, aging and increased Scarff, Bloom and Richardson grade, but is not associated with triple-negative and basal-like status. Subsequent data mining across multiple large databases demonstrated a positive association between MUC1 mRNA expression and cyclic AMP-responsive element-binding protein 3-like 4 (CREB3L4) in breast cancer tissues. The present data indicated that the overexpression of MUC1 indicates a poor prognosis in patients with breast cancer and is associated with MUC1 promoter methylation status. Additionally, MUC1 positively correlated with CREB3L4 and may serve as a potential prognostic factor and therapy target for breast cancer.

Expression and function of MUC1 in uterine tissues during early pregnancy in sheep after natural oestrous or artificially-induced oestrous

Mucin 1 (MUC1), a cell surface glycoprotein, is expressed mainly in the endometrial luminal epithelium (LE) and glandular epithelium (GE) of the endometrium in many mammalian species including mice, rats, pigs, sheep, horses and humans during various stages of a menstrual or oestrous cycle, where it plays an important role in embryo implantation and placentation. However, the expression and function of MUC1 in uterine tissues during early pregnancy in sheep after artificially-induced oestrous is not known. Therefore, we investigated the expression and function of MUC1 in the early pregnant and non-pregnant uterine tissues of sheep with natural oestrous or artificially-induced oestrous on days 10, 12, 14, 16 and 18 of the cycle by in situ hybridization, quantitative real-time polymerase chain reaction, immunohistochemical staining and western blotting methods. According to our results, MUC1 mRNA and protein expression increased initially but then decreased from days 10–18, peaking on day 14 in the uterine tissues of non-pregnant ewes after both natural and artificially-induced oestrous. MUC1 protein localisation was observed in the LE on days 10, 12 and 14 and in the GE on days 16 and 18. In contrast, MUC1 mRNA and protein expression increased on days 10 and 12, decreased on day 14, but increased again on days 16 and 18 in the uterine tissues of pregnant ewes both in natural oestrous and in artificially-induced oestrous. Additionally, the MUC1 mRNA and protein expression levels in the uterine tissues of the early pregnant sheep were significantly lower than those in the non-pregnant sheep on days 10, 14, and 18, except on day 16(P < 0.01). Enhancing MUC1 protein expression with oestrogen or/and progesterone decreased the blastocyst adhesion rate when blastocysts were co-cultured with endometrial epithelial cells (EECs), while inhibiting MUC1 protein expression with IFN-τ increased the blastocyst adhesion rate when the blastocysts were co-cultured with EECs. Compared with the ewes undergoing natural oestrus, the expression trend and regulation of MUC1 did not change, and the MUC1 expression levels only increased under artificial oestrus conditions. Our data provide important information for improving the conception rate in sheep undergoing artificially-induced oestrus and offer some reference points relating to embryo transfer, oestrus synchronisation and superovulation.

Regulation of Mucin 1 and multidrug resistance protein 1 by honokiol enhances the efficacy of doxorubicin-mediated growth suppression in mammary carcinoma cells.

Understanding the link between chemoresistance and cancer progression may identify future targeted therapy for breast cancer. One of the mechanisms by which chemoresistance is attained in cancer cells is mediated through the expression of multidrug resistance proteins (MRPs). Acquiring drug resistance has been correlated to the emergence of metastasis, accounting for the progression of the disease. One of the diagnostic markers of metastatic progression is the overexpression of a transmembrane protein called Mucin 1 (MUC1) which has been implicated in reduced survival rate. The objective of this study was to understand the relationship between MUC1 and MRP1 using natural phenolic compound isolated from Magnolia grandiflora, honokiol, in mammary carcinoma cells. We provide evidence that honokiol suppresses the expression level of MUC1 and MRP1 in mammary carcinoma cells. In a time-dependent manner, honokiol-mediated reduction of MUC1 is followed by a reduction of MRP1 expression in the breast cancer cells. Additionally, silencing MUC1 suppresses the expression level of MRP1 and enhances the efficacy of doxorubicin, an MRP1 substrate. Taken together, these findings suggest MUC1 regulates the expression of MRP1 and provides a direct link between cancer progression and chemoresistance in mammary carcinoma cells.

Abstract 735: Honokiol enhances the anticancer effects of doxorubicin by regulating Mucin 1 and Multidrug resistance-associated protein 1 (MRP1) in mammary carcinoma MDA-MB-231 cells

Abstract Although great progress has been made in the treatment of breast cancer, resistance to chemotherapeutic drugs is a problem facing current cancer research, promoting the need to understand the molecular mechanisms involved in breast cancer and identify future targeted therapy. One of the mechanisms by which chemoresistance is attained in cancer cells is mediated through the expression of MDR-related proteins (MRPs). These transmembrane proteins efflux drugs across the plasma membrane, conferring resistance of cancer cells to anticancer drugs. Acquiring drug resistance has been correlated to the emergence of metastasis, accounting for two factors that may be related to progression of the disease. One of the diagnostic markers of metastatic progression is Mucin 1 (MUC1), an oncoprotein which has been implicated in reduced survival rate. Interaction of MUC1 with MRP-1 promotes resistance to conventional chemotherapeutic drugs. While several inhibitors have been identified and characterized to overcome drug resistance, thus far none of these have led to effectively managing acquired drug resistance. Along with existing drug treatments for breast cancer, the focus of clinicians and researchers have shifted towards exploring natural products to treat alone or in combination with chemotherapeutic agents to enhance the efficacy of these drugs in cancer. One such compound is honokiol, a natural phenolic compound extracted from Magnolia grandiflora that suppresses breast carcinogenesis in vitro and in vivo. The purpose of the current study is to determine whether honokiol regulates MUC1 and MRP1 in mammary carcinoma cells, MDA-MB-231, and the role of honokiol to enhance the efficacy of chemotherapeutic agent, doxorubicin. We investigated the effects of honokiol on the expression of MUC1 and MRP1 in MDA-MB-231 cells by RT-PCR and Immunoblotting. Cell proliferation assays (MTT-(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) were used to study the effect of honokiol on doxorubicin-mediated growth suppression. Honokiol suppressed mRNA and protein expression levels of MUC1 and MRP1 in MDA-MB-231 cells. In addition, honokiol suppressed the growth of mammary carcinoma MDA-MB-231 cells, and enhanced the efficacy of doxorubicin-mediated mammary carcinoma growth suppression. Taken together, suppressing the expression level of MUC1 and MRP1 by honokiol enhances the effect of conventional chemotherapeutic drugs. Citation Format: Padmamalini Thulasiraman, Saad Alshareedah. Honokiol enhances the anticancer effects of doxorubicin by regulating Mucin 1 and Multidrug resistance-associated protein 1 (MRP1) in mammary carcinoma MDA-MB-231 cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 735. doi:10.1158/1538-7445.AM2015-735

Increased expression of MUC1 predicts poor survival in salivary gland mucoepidermoid carcinoma

BackgroundMucoepidermoid carcinoma (MEC) is a malignant neoplasm that originates most commonly in the major and minor salivary glands. The aim of this study is to determine the relationship between mucin-1 (MUC1) expression and patient outcome based on a large number of cases. Patients and methodsSurgical specimens from 357 patients with primary salivary gland MEC and 10 patients with normal salivary gland tissue were examined by immunohistochemistry. The relationship between MUC1 expression and the clinicopathological data and patient survival was analyzed. ResultsResults showed that MUC1 expression level was higher in MEC tissues than in paired normal tissues (P = 0.001), and the expression level of MUC1 was significantly associated with gender (P = 0.02), location (P = 0.001), grade (P = 0.001), stage (P = 0.0018) and lymph node metastasis (P = 0.001). In addition, increased expression of MUC1 was confirmed as a strong predictor of poor survival in salivary gland MEC (HR 2.175 [95% CI 1.263, 3.745]; P = 0.0051). ConclusionThe findings indicate that an increased expression of MUC1 may be of great value in assessing the development and prognosis of salivary gland MEC, and could be used as a new molecule target to improve outcomes for these patients in the future.

Expression of Mucin 1 (MUC1) in Benign, Premalignant and Malignant Vulvar Tumors.

We investigated mucin 1(MUC1) expression in 10 vulvar condyloma acuminata(VCA), 15 vulvar intraepithelial neoplasia(VIN) and 30 vulvar squamous cell carcinomas (VSCC) using three different monoclonal antibodies(Ma695, CA15−3, and DF3), and compared the level of MUC1 expression with the clinicopathologic features of VSCC. Of the three monoclonal antibodies, Ma695 showed the strongest immunoreactivity. MUC1 expression levels were high in VSCC, low in VIN III, and undetectable in VIN I-II, VCA and normal vulvar epithelium. Patients with human papilloma virus(HPV)−negative VSCC showed higher MUC1 expression than HPV−positive patients. The MUC1 expression level gradually increased from well through moderately to poorly differentiated VSCC, and there was a statistically significant difference between moderately/poorly differentiated VSCC and well differentiated VSCC(p<0.05). These results indicate that MUC1 expression may be an effective tumor marker for VSCC, and suggest that MUC1 gene expression may be a late event in the growth of VSCC. Moreover, it appears likely that MUC1 expression correlates negatively with HPV infection. Since the appearance of MUC1 is linked to cell dedifferentiation, it may be related to the malignant transformation and progression of VSCC.