Mitochondrial NDUFA4L2 protein promotes the vitality of lung cancer cells by repressing oxidative stress

Meng, Lifei; Yang, Xuhui; Xie, Xian-Jin; Wang, Mingsong

doi:10.1111/1759-7714.12984

Cited by 30 publications

(33 citation statements)

References 36 publications

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“…For hepatocellular carcinoma, Sarathi et al found that NDUFA4L2, CRHBP and PIGU were main genes with monotonic changes of expression across cancer stages that are expected to be the therapeutic targets [ 21 ]. And in non-small cell lung cancer, some researchers also discovered that mitochondrial NDUFA4L2 protein promotes the vitality of lung cancer cells by repressing oxidative stress, suggesting mitochondrial NDUFA4L2 could represent promising targets for therapy [ 22 ]. Unlike SHMT2, NDUFA4L2 had been reported to be involved in the occurrence and development of kidney cancer.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the clinical significance of SHMT2 and its co-expressed gene in human kidney cancer

Wang

Chong

et al. 2020

Biol Res

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Background Kidney cancer is one of the most common cancers in the world. It is necessary to clarify its underlying mechanism and find its prognostic biomarkers. Current studies showed that SHMT2 may be participated in several kinds of cancer. Methods Our studies investigated the expression of SHMT2 in kidney cancer by Oncomine, Human Protein Atlas database and ULCAN database. Meanwhile, we found its co-expression gene by cBioPortal online tool and validated their relationship in A498 and ACHN cells by cell transfection, western blot and qRT-PCR. Besides these, we also explored their prognostic values via the Kaplan–Meier plotter database in different types of kidney cancer patients. Results SHMT2 was found to be increased in 7 kidney cancer datasets, compared to normal renal tissues. For the cancer stages, ages and races, there existed significant difference in the expression of SHMT2 among different groups by mining of the UALCAN database. High SHMT2 expression is associated with poor overall survival in patients with kidney cancer. Among all co-expressed genes, NDUFA4L2 and SHMT2 had a high co-expression efficient. SHMT2 overexpression led to the increased expression of NDUFA4L2 at both mRNA and protein levels. Like SHMT2, overexpressed NDUFA4L2 also was associated with worse overall survival in patients with kidney cancer. Conclusion Based on above results, overexpressed SHMT2 and its co-expressed gene NDUFA4L2 were all correlated with the prognosis in kidney cancer. The present study might be benefit for better understanding the clinical significance of SHMT2 and provided a potential therapeutic target for kidney cancer in future.

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Section: Discussionmentioning

confidence: 99%

Evaluating the clinical significance of SHMT2 and its co-expressed gene in human kidney cancer

Wang

Chong

et al. 2020

Biol Res

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“…Wherein, activated by HIF1α, NDUFA4L2 inhibited ROS production by the respiratory chain of mitochondria in non-small cell lung cancer cells. Knockdown of NDUFA4L2 promoted an increase in ROS production, apoptosis, and the progression of EMT in the NSCLC cell lines [45]. Apparently, the activation of EMT due to a decrease in the expression level of NDUFA4L2 is a mechanism of its influence on metastasis of ccRCC.…”

Section: Discussionmentioning

confidence: 86%

The Genes—Candidates for Prognostic Markers of Metastasis by Expression Level in Clear Cell Renal Cell Cancer

et al. 2020

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The molecular prognostic markers of metastasis are important for personalized approaches to clear cell renal cell carcinoma (ccRCC) treatment but markers for practical use are still missing. To address this gap we studied the expression of ten genes—CA9, NDUFA4L2, VWF, IGFBP3, BHLHE41, EGLN3, SAA1, CSF1R, C1QA, and FN1—through RT-PCR, in 56 ccRCC patients without metastases and with metastases. All of these, excluding CSF1R, showed differential and increased (besides SAA1) expression in non-metastasis tumors. The gene expression levels in metastasis tumors were decreased, besides CSF1R, FN1 (not changed), and SAA1 (increased). There were significant associations of the differentially expressed genes with ccRCC metastasis by ROC analysis and the Fisher exact test. The association of the NDUFA4L2, VWF, EGLN3, SAA1, and C1QA expression with ccRCC metastasis is shown for the first time. The CA9, NDUFA4L2, BHLHE4, and EGLN3 were distinguished as the strongest candidates for ccRCC metastasis biomarkers. We used an approach that presupposed that the metastasis marker was the expression levels of any three genes from the selected panel and received sensitivity (88%) and specificity (73%) levels with a relative risk of RR > 3. In conclusion, a panel of selected genes—the candidates in biomarkers of ccRCC metastasis—was created for the first time. The results might shed some light on the ccRCC metastasis processes.

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“…As a component of the ETC complex I subunit, NDUFA4L2 ne-tunes complex I activity, and mediates mitochondrial activation of OXPHOS [45]. COX6B2 facilitates the assembly of complex IV to support mitochondrial respiration and OXPHOS-induced generation of ATP [46]. We also found the upregulation of ATP6V1G2, which encoded subunit G2 of vacuolar ATPase (V-ATPase), transporting protons from the cytoplasm into the lysosome and maintaining lysosomal acidi cation [47].…”

Section: Fp Intervention Promoted Energy Metabolism Of the Colonic Epmentioning

confidence: 80%

Flaxseed Polysaccharide Altering Colonic Gene Expression of Lipid Metabolism and Energy Metabolism in Obese Rat

Lin¹,

Qi²,

Zhang³

et al. 2020

Preprint

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BackgroundObesity is one of the most serious public health challenges. Recently, we found that flaxseed polysaccharide (FP) had an anti-obesity effect through promoting lipid metabolism, inducing satiety and regulating gut microbiota, but how FP promote lipid metabolism through altering the colonic epithelial cells remains to be elucidated. In this study, a transcriptome study was performed to investigate the effect of FP altering the gene expression of colonic epithelial cells in an obese rat model. ResultsThe transcriptome analysis showed that 3,785 genes were differentially expressed after FP intervention in colonic epithelial cells, including 374 down-regulated and 3,411 up-regulated genes. Through KEGG analysis, we found out three classical pathways related to lipid metabolism and energy metabolism, including PPAR signaling pathway, nitrogen metabolism and oxidative phosphorylation (OXPHOS). Moreover, qRT-PCR results showed consistent expression trends of differential genes with transcriptome analysis. ConclusionsThe anti-obesity effect of FP may be achieved by regulating the expression of lipid metabolism- and energy metabolism-related proteins acting on the PPAR (peroxisome proliferator-activated receptor) signaling pathway, nitrogen metabolism and OXPHOS pathway in vivo.

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Mitochondrial NDUFA4L2 protein promotes the vitality of lung cancer cells by repressing oxidative stress

Cited by 30 publications

References 36 publications

Evaluating the clinical significance of SHMT2 and its co-expressed gene in human kidney cancer

Evaluating the clinical significance of SHMT2 and its co-expressed gene in human kidney cancer

The Genes—Candidates for Prognostic Markers of Metastasis by Expression Level in Clear Cell Renal Cell Cancer

Flaxseed Polysaccharide Altering Colonic Gene Expression of Lipid Metabolism and Energy Metabolism in Obese Rat

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