Background Mitochondrial transcription elongation factor (TEFM) is a key molecule for mitochondrial DNA (mtDNA) replication-transcription switch. TEFM regulates both transcription elongation and RNA processing in mitochondria. However, the expression level and prognostic value of TEFM in low grade glioma (LGG) remain unclear. Therefore, in this study, we aimed to evaluate the clinical significance and the prognostic value of TEFM in LGG based on publicly available data. Methods The relative mRNA expression level of TEFM in non-tumor brain tissues and LGG tissues were retrieved from Gene Expression Profiling Interactive Analysis (GEPIA). The RNA-Seq expression of TEFM and clinical information in LGG patients were collected from the updated the Cancer Genome Atlas (TCGA) database by using R3.6.1 software. Next, the relationship between the mRNA expression of TEFM and clinicopathological characteristics were analyzed. Kaplan-Meier survival curves of overall survival (OS) and disease-free survival (DFS) were implemented for the relationship between the mRNA expression of TEFM and the prognosis of LGG patients. A Cox regression model was performed for the multivariate analysis of the factors affected the prognosis of LGG patients. GEPIA online tool was used to analyze the correlation between TEFM gene expression level and other related mitochondrial regulatory genes in LGG. Finally, The Gene Set Enrichment Analysis (GSEA) was performed to identify cell processes and molecular signaling cascades affected by TEFM. Results GEPIA analysis showed that the mRNA expression levels of TEFM in LGG were significantly higher than that of non-tumor tissue. Moreover, the mRNA expression of TEFM is significantly correlated with age, World Health Organization (WHO) grade, pathological types, headache history and supratentorial location (P<0.05). Kaplan-Meier analysis showed that a high expression level of TEFM mRNA indicated a poor prognosis in OS rate (log-rank, P<0.01). Multivariate Cox regression analysis showed that age, WHO grade, pathological types and supratentorial location were the independent prognostic factors of LGG patients. The mRNA expression levels of TEFM gene were positively correlated with the TFAM , TFB1M , TFB2M , MTERF1–F4 and NRF1 gene (P<0.01, R>0), but negatively correlated with the POLRMT gene (P<0.01, R=−0.18) in LGG. The GSEA revealed that genes associated with the cell cycle, RNA degradation, spliceosome, and ubiquitin mediated proteolysis signaling pathway were remarkably enriched in higher-TEFM versus lower-TEFM tumors. Conclusions Our findings disclosed that the expression of TEFM mRNA was significantly upregulated in human LGG tissues compared to non-tumor brain tissues. More importantly, the elevated expression ...
Background Mitochondrial transcription termination factor 3 (MTERF3) is a negative regulator of mitochondrial transcription. It is a modular factor involves in mitochondrial ribosome biogenesis and protein synthesis. However, the association between MTERF3 and breast cancers remains largely unknown. The aim of this study was to investigate the expression of MTERF3 in breast carcinoma and to analyze its clinicopathological significance, and to examine the potential prognostic value of MTERF3 in breast cancer. Methods The protein expression levels of MTERF3 in MCF7 (Luminal A), BT-474 (Luminal B), SKBR3 (HER2 overexpression), MDA-MB-468 (Basal like) and MCF10A cell lines were detected by Western blotting. Immunohistochemistry (IHC), Western blotting, and semiquantitative RT-PCR were performed to analyze the protein and mRNA expression levels of MTERF3 in 58 breast cancer tissues and 58 noncancerous breast tissues. The MTERF3 expression data and clinical information from breast cancer patients were downloaded from the TCGA dataset by using the R3.6.1 software. Then the relationship between the expression level of MTERF3 and clinicopathological characteristics and the prognostic value was analyzed. A Cox regression model was performed for the multivariate analysis of the factors that affected the prognosis of breast cancer. The association between the expression levels of MTERF3 and other mitochondrial regulatory genes was analyzed with GEPIA. Results MTERF3 is upregulated in breast cancer cell lines compared to noncancerous breast cell line. The IHC results showed that the MTERF3 protein was located in the cytoplasm, and the rate of positive expression in breast cancer tissue was significantly upregulated compared with the adjacent normal tissue. The mRNA and protein expression levels of MTERF3 in breast cancer tissues were significantly higher than that in breast tissues. Moreover, the expression of MTERF3 was significantly correlated with ER status, PR status, breast cancer molecular typing, cancer type, histological diagnosis and primary site (P<0.05). Further analysis showed MTERF3 expression was not related to prognosis. Multivariate Cox regression analysis showed that age, metastasis status and tumor type were independent prognostic factors for breast cancer patients. The expression levels of MTERF3 were positively correlated with the TFAM , TFB1M , TFB2M , MTERF1 , TEFM and MFN1 genes but negatively correlated with the MTERF4 and PINK1 genes. In addition, the expression levels of MTERF3 were not correlated with the MTERF2 gene. Conclusions MTERF3 was significantly upregulated in breast cancer cells and tissues compared with noncancerous cells and tissues. Moreover, th...
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