Knockdown of TMEM45A overcomes multidrug resistance and epithelial–mesenchymal transition in human colorectal cancer cells through inhibition of TGF‐β signalling pathway

Zhu, Mo; Jiang, Baofei; Yan, Dongsheng; Wang, Xiaopeng; Ge, Hengfa; Sun, Yueming

doi:10.1111/1440-1681.13220

Cited by 13 publications

(10 citation statements)

References 60 publications

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“… 26 Zhu et al demonstrated that knockdown of TMEM45A suppressed multi-drug resistance-enhanced migration, invasion and EMT in human colorectal cancer cells by inhibiting the transforming growth factor beta (TGF-β) signalling pathway. 27 Consistently, the results of the GSEA performed in our study revealed that high expression of TMEM45A was associated with EMT, and the wound-healing assay confirmed that knockdown of TMEM45A inhibited the migration ability of ccRCC cells in vitro. Furthermore, we identified a significant relationship between TMEM45A and EMT in 32 of the 33 cancer types in the pan-cancer analysis.…”

Section: Discussionsupporting

confidence: 87%

Upregulation of TMEM45A Promoted the Progression of Clear Cell Renal Cell Carcinoma in vitro

Jiang¹,

Chen²,

Wan³

et al. 2021

JIR

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Background Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive type of primary kidney cancer worldwide. Transmembrane protein 45A (TMEM45A) has been reported to be closely associated with the progression of several cancers. However, the role of TMEM45A in ccRCC remains unclear. Our study intended to explore the potential role of TMEM45A in ccRCC. Methods Data on the expression of TMEM45A were obtained from multiple databases, including UCSC, GEPIA2, Oncomine and TIMER. Real-world samples of ccRCC and paired normal renal tissues were used to confirm the information obtained from the databases. In addition, the prognostic value of TMEM45A was evaluated. Loss-of-function assays were performed using TMEM45A-targeting lentivirus to evaluate the biological role of TMEM45A in renal cancer cells. Gene set enrichment analysis (GSEA) was performed to investigate the potential molecular mechanisms. Results TMEM45A was significantly overexpressed in patients with ccRCC and correlated with poor overall survival and disease-free survival. In addition, the expression of TMEM45A was closely associated with various clinicopathological parameters such as histological grade and TNM stage. Knockdown of TMEM45A inhibited the proliferation and migration and promoted the apoptosis of ccRCC cells in vitro. The results of the GSEA suggested that TMEM45A was potentially involved in the promotion of epithelial–mesenchymal transition (EMT) and inflammatory response in ccRCC. Conclusion TMEM45A was overexpressed and associated with poor survival and acted as a tumour promoter in ccRCC; therefore, might be a potential prognostic marker and therapeutic target.

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Section: Discussionsupporting

confidence: 87%

Upregulation of TMEM45A Promoted the Progression of Clear Cell Renal Cell Carcinoma in vitro

Jiang¹,

Chen²,

Wan³

et al. 2021

JIR

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“…TMEM45A protein expression has been published in several cancer cell lines, such as MDA-MB-231 breast cancer cells and in HepG2 human hepatoma cells [ 44 ], and in several other cancers such as human cervical lesions [ 69 ], ovarian cancer [ 70 ], glioma [ 71 , 72 ], renal cell carcinoma [ 73 , 74 , 75 ], colorectal cancer [ 76 ], head and neck cancer [ 75 ], and invasive breast cancer [ 77 ]. In our previous work, we reported the increased cell-surface expression of TMEM45A in three-dimensional cultures of A549 cells and in murine A549 xenograft tumors by CyTOF [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Single-Cell Heterogeneity of Adenocarcinoma Cell Lines and the Investigation of Intratumor Heterogeneity Reveals the Expression of Transmembrane Protein 45A (TMEM45A) in Lung Adenocarcinoma Cancer Patients

Neuperger

Balog

Tiszlavicz

et al. 2021

Cancers

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Intratumoral heterogeneity (ITH) is responsible for the majority of difficulties encountered in the treatment of lung-cancer patients. Therefore, the heterogeneity of NSCLC cell lines and primary lung adenocarcinoma was investigated by single-cell mass cytometry (CyTOF). First, we studied the single-cell heterogeneity of frequent NSCLC adenocarcinoma models, such as A549, H1975, and H1650. The intra- and inter-cell-line single-cell heterogeneity is represented in the expression patterns of 13 markers—namely GLUT1, MCT4, CA9, TMEM45A, CD66, CD274 (PD-L1), CD24, CD326 (EpCAM), pan-keratin, TRA-1-60, galectin-3, galectin-1, and EGFR. The qRT-PCR and CyTOF analyses revealed that a hypoxic microenvironment and altered metabolism may influence cell-line heterogeneity. Additionally, human primary lung adenocarcinoma and non-involved healthy lung tissue biopsies were homogenized to prepare a single-cell suspension for CyTOF analysis. The CyTOF showed the ITH of human primary lung adenocarcinoma for 14 markers; particularly, the higher expressions of GLUT1, MCT4, CA9, TMEM45A, and CD66 were associated with the lung-tumor tissue. Our single-cell results are the first to demonstrate TMEM45A expression in human lung adenocarcinoma, which was verified by immunohistochemistry.

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“…It also affects the proliferation and invasion of human ovarian cancer and glioma cells [64][65][66][67]. TMEM45A gene knockdown has been found to be effective in inhibiting multidrug resistance and suppressing EMT by inhibiting the TGF-β signaling pathway in human colorectal cancer cells [68]. These studies suggest that TMEM45A may be a potential biomarker.…”

Section: Discussionmentioning

confidence: 99%

Identification and clinical validation of EMT-associated prognostic features based on hepatocellular carcinoma

Wang

et al. 2021

Cancer Cell Int

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Background The aim of this study was to construct a model based on the prognostic features associated with epithelial–mesenchymal transition (EMT) to explore the various mechanisms and therapeutic strategies available for the treatment of metastasis and invasion by hepatocellular carcinoma (HCC) cells. Methods EMT-associated genes were identified, and their molecular subtypes were determined by consistent clustering analysis. The differentially expressed genes (DEGs) among the molecular subtypes were ascertained using the limma package and they were subjected to functional enrichment analysis. The immune cell scores of the molecular subtypes were evaluated using ESTIMATE, MCPcounter, and GSCA packages of R. A multi-gene prognostic model was constructed using lasso regression, and the immunotherapeutic effects of the model were analyzed using the Imvigor210 cohort. In addition, immunohistochemical analysis was performed on a cohort of HCC tissue to validate gene expression. Results Based on the 59 EMT-associated genes identified, the 365—liver hepatocellular carcinoma (LIHC) samples were divided into two subtypes, C1 and C2. The C1 subtype mostly showed poor prognosis, had higher immune scores compared to the C2 subtype, and showed greater correlation with pathways of tumor progression. A four-gene signature construct was fabricated based on the 1130 DEGs among the subtypes. The construct was highly robust and showed stable predictive efficacy when validated using datasets from different platforms (HCCDB18 and GSE14520). Additionally, compared to currently existing models, our model demonstrated better performance. The results of the immunotherapy cohort showed that patients in the low-risk group have a better immune response, leading to a better patient’s prognosis. Immunohistochemical analysis revealed that the expression levels of the FTCD, PON1, and TMEM45A were significantly over-expressed in 41 normal samples compared to HCC samples, while that of the G6PD was significantly over-expressed in cancerous tissues. Conclusions The four-gene signature construct fabricated based on the EMT-associated genes provides valuable information to further study the pathogenesis and clinical management of HCC.

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Knockdown of TMEM45A overcomes multidrug resistance and epithelial–mesenchymal transition in human colorectal cancer cells through inhibition of TGF‐β signalling pathway

Cited by 13 publications

References 60 publications

Upregulation of TMEM45A Promoted the Progression of Clear Cell Renal Cell Carcinoma in vitro

Upregulation of TMEM45A Promoted the Progression of Clear Cell Renal Cell Carcinoma in vitro

Analysis of the Single-Cell Heterogeneity of Adenocarcinoma Cell Lines and the Investigation of Intratumor Heterogeneity Reveals the Expression of Transmembrane Protein 45A (TMEM45A) in Lung Adenocarcinoma Cancer Patients

Identification and clinical validation of EMT-associated prognostic features based on hepatocellular carcinoma

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