Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study

Rogler, Anja; Hoja, S; Giedl, Johannes; Ekici, Arif B.; Wach, Sven; Täubert, Helge; Goebell, Peter J.; Wullich, Bernd; Stöckle, Michael; Lehmann, Jan; Petsch, S.; Hartmann, Arndt; Stoehr, Robert

doi:10.1186/1471-2407-14-214

Cited by 19 publications

(14 citation statements)

References 34 publications

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“…Some candidate oncogenes and tumor suppressors have been identified among these amplified and deleted loci and have characterized using this approach. For example, the MTUS1 and SFRP1 genes on chromosome 8p22 and 8p12-11.1 loci have been identified for their tumor suppression function in UBUC [ 17 , 18 ]. Regarding chromosome 8q, our results are consistent with those of previous studies which have reported gains involving chromosome 8q as one of the most common events in UBUC.…”

Section: Discussionmentioning

confidence: 99%

CEBPDamplification and overexpression in urothelial carcinoma: a driver of tumor metastasis indicating adverse prognosis

Wang

et al. 2015

Oncotarget

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The molecular aberrations responsible for the progression of urothelial carcinoma (UC) remain largely obscure. To search candidate driver oncogenes in UC, we performed array-based genomic hybridization (aCGH) on 40 UBUC samples. Amplification of 8q11.21 was preferentially identified in patients who developed disease-specific death (53.8%) and distal metastasis (50.0%) but was barely detected in non-eventful cases (3.7% and 0%, respectively). In order to quantify the expression of candidate genes harbored in 8q11.21, laser-capture microdissection coupled with RT-PCR was performed on 32 of the 40 cases submitted to aCGH. With this, we identified CEBPD mRNA expression as most significantly associated with gains of 8q11.21, suggesting amplification-driven expression. By performing CEBPD-specific FISH and immunohistochemistry on 295 UBUCs, we confirmed CEBPD amplification (21.3%) and overexpression (29.8%) were strongly related to each other (p<0.001). Moreover, both were associated with adverse clinicopathologic features and worse outcomes. Furthermore, the clinical significance of CEBPD expression was also confirmed in an independent cohort comprised of 340 UCs from the upper urinary tract. Interestingly, CEBPD knockdown suppressed cell proliferation, migration and, most significantly, cell invasion ability in UC cells. The latter phenotype is attributed to downregulation of MMP2 as identified by RT2 Profiler PCR array. Moreover, expression of CEBPD significantly enhanced MMP2 expression and transcriptional activation by directly binding to its promoter region, as confirmed by promoter reporter assay and chromatin immunoprecipitation assay. Conclusively, CEBPD amplification is a mechanism driving increased mRNA and protein expression that confers aggressiveness in UC through MMP2-mediated cell invasiveness.

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Section: Discussionmentioning

confidence: 99%

CEBPDamplification and overexpression in urothelial carcinoma: a driver of tumor metastasis indicating adverse prognosis

Wang

et al. 2015

Oncotarget

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“…MTUS1 is localized at chromosome 8p22 and comprises 17 exons 47 . Downregulation or loss of MTUS1 is a frequent event and indicator of poor survival in bladder carcinomas, lung cancer, salivary adenoid cystic carcinoma, gastric cancer, and breast cancer [48][49][50][51][52] . In addition, depletion of MTUS1 increases microtubule dynamics and contributes to metastasis in breast cancer 19 .…”

Section: Discussionmentioning

confidence: 99%

RNA-binding protein SORBS2 suppresses clear cell renal cell carcinoma metastasis by enhancing MTUS1 mRNA stability

Fan

Zhou³

et al. 2020

Cell Death Dis

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RNA-binding proteins (RBPs) predominantly contribute to abnormal posttranscriptional gene modulation and disease progression in cancer. Sorbin and SH3 domain-containing 2 (SORBS2), an RBP, has been reported to be a potent tumor suppressor in several cancer types. Through integrative analysis of clinical specimens, we disclosed that the expression level of SORBS2 was saliently decreased in metastatic tissues and positively correlated with overall survival. We observed that overexpression of SORBS2 brought about decreased metastatic capacity in ccRCC cell lines. Transcriptome-wide analysis revealed that SORBS2 notably increased microtubule-associated tumor-suppressor 1 gene (MTUS1) expression. In-depth mechanistic exploring discovered that the Cys2-His2 zinc finger (C2H2-ZnF) domain of SORBS2 directly bound to the 3′ untranslated region (3′UTR) of MTUS1 mRNA, which increased MTUS1 mRNA stability. In addition, we identified that MTUS1 regulated microtubule dynamics via promoting KIF2CS192 phosphorylation by Aurora B. Together, our research identified SORBS2 as a suppressor of ccRCC metastasis by enhancing MTUS1 mRNA stability, providing a novel understanding of RBPs during ccRCC progression.

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“…Nevertheless, GBC remains aggressive, needing new biomarkers. MTUS1 is a tumor-suppressor gene as was shown in several studies (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Thus, the expression of MTUS1 protein and mRNA in tumor tissues was significantly lower than that in normal tissues of several human tumor types, including breast cancer, gastric carcinoma, head and neck squamous cell carcinoma, salivary adenoid cystic carcinoma, and urinary bladder cancer (8,11,13,16,17).…”

Section: Kaplan-meier Analysis For Cancer-specific (A) and Disease-mentioning

confidence: 88%

“…Thus, the expression of MTUS1 protein and mRNA in tumor tissues was significantly lower than that in normal tissues of several human tumor types, including breast cancer, gastric carcinoma, head and neck squamous cell carcinoma, salivary adenoid cystic carcinoma, and urinary bladder cancer (8,11,13,16,17). In bladder carcinoma, the expression of MTUS1 protein was reduced in papillary and advanced bladder carcinomas (7). Low expression of MTUS1 was correlated with adverse clinical outcome.…”

Section: Kaplan-meier Analysis For Cancer-specific (A) and Disease-mentioning

confidence: 96%

Loss of MTUS1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Carcinoma

Sim¹,

Kim²,

Kim³

et al. 2019

In Vivo

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Background/Aim: Microtubule-associated scaffold protein 1 (MTUS1) acts as tumor suppressor in several cancer types. This study assessed the relationship between clinicopathological characteristics and expression of microRNA candidates based on MTUS1 expression in gallbladder cancer (GBC). Materials and Methods: MTUS1 expression was evaluated by immunohistochemical staining of tissue microarrays from 109 cases of GBC. The association of MTUS1 expression with clinicopathological factors was explored. Two microRNA candidates (miR-19a-3p, and miR-19b-3p), which were identified by a literature review and computational analysis, were assessed in GBC tissue samples by quantitative real-time polymerase chain reaction. Results: Low MTUS1 expression in GBC was associated with high histological grade, perineural invasion, lymphovascular invasion, high T-stage, advanced TNM stage, poorer disease-free survival, and poorer cancer-specific survival. No statistical association between MTUS1 expression and expression of microRNA candidates was observed. Conclusion: MTUS1 may act as tumor suppressor and might be a potential biomarker for predicting prognosis in GBC. Although gallbladder cancer (GBC) is rare, it is the most common malignant tumor of the biliary tract (1-4). No specific symptoms or reliable diagnostic markers are established for GBC. In addition, GBC is diagnosed late; moreover, systemic chemotherapy and radiation therapy do not produce significant improvement in survival or quality of life for patients with GBC (1-3). Thus, patients with GBC do not have a favorable clinical outcome (1-3). Therefore, it is essential to evaluate new biomarkers for predicting the prognosis of patients with GBC. Microtubule-associated scaffold protein 1 (MTUS1), also known as angiotensin II receptor-interacting protein (ATIP), is located on chromosome 8p22 and contains 17 exons (5, 6). MTUS1 acts as a tumor-suppressor gene, exhibiting low expression in a variety of malignancies, including breast, colorectal, head and neck, ovary, stomach, salivary gland, and urinary bladder cancer (7-18). MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression by binding target mRNA at the post-transcriptional level. As miRNA pairing targets mRNAs in an imperfect manner, a single miRNA can target multiple genes; and one gene may be affected by multiple miRNAs (1, 19, 20). Recently, Ge et al. demonstrated that miR-19a and miR-19b co-regulate MTUS1 in lung cancer (14). Kara et al. reported decreased MTUS1 expression and elevated miR-183-5p expression in advanced stages of breast cancer (10). Additionally, several miRNAs including miR-135b-5p, miR-373-3p, miR-183-5p, miR-142-5p, miR-200c-3p, and miR-19a-3p, may play important roles in colorectal carcinoma through MTUS1 (21). The role of MTUS1 as a tumor suppressor has been reported, however, the expression of MTUS1 and its clinicopathological significance in GBC has not yet been evaluated. Thus, this study aimed to assess the clinicopathological parameters in association with MTUS1 expr...

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Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study

Cited by 19 publications

References 34 publications

CEBPDamplification and overexpression in urothelial carcinoma: a driver of tumor metastasis indicating adverse prognosis

CEBPDamplification and overexpression in urothelial carcinoma: a driver of tumor metastasis indicating adverse prognosis

RNA-binding protein SORBS2 suppresses clear cell renal cell carcinoma metastasis by enhancing MTUS1 mRNA stability

Loss of MTUS1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Carcinoma

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