Identification of alternatively spliced GRIM-19 mRNA in kidney cancer tissues

He, Xuelian; Cao, Xinmin

doi:10.1038/jhg.2010.57

Cited by 15 publications

(9 citation statements)

References 27 publications

(33 reference statements)

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“…5D). This could of course be due to sensitivity issues of the anti-GRIM-19 antibody or that the protein is completely lost but it could also suggest a defective protein, as suggested in [27]. The antibody used in our study recognizes the full-length protein and the reason for the absent signal in the western blot analyses could be inability of the antibody to recognize any modified form of the protein.…”

Section: Resultsmentioning

confidence: 86%

Differentially Expressed Proteins in Malignant and Benign Adrenocortical Tumors

et al. 2014

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We have compared the microsomal protein composition of eight malignant and six benign adrenocortical tumors with proteomic methods. IGF2 had increased level in the malignant tumors, confirming previous microarray studies on the same material. Aldolase A, a glycolytic enzyme, also showed increased levels in the malignant tissue compared to the benign. Additionally, several proteins belonging to complex I in the mitochondrial respiration chain showed decreased levels in the malignant tissue. Taken together, this may indicate a shift in energy metabolism where glycolysis may be favored over tight coupling of glycolysis and mitochondrial respiration, a phenomenon known as the Warburg effect. One of the complex I proteins that showed decreased levels in the malignant tissue was GRIM-19. This protein has been suggested as a tumor suppressive protein by being a negative regulator of STAT3. In summary, an analysis of the microsomal proteome in adrenocortical tumors identifies groups of proteins as well as specific proteins differentially expressed in the benign and malignant forms. These proteins shed light on the biology behind malignancy and could delineate future drug targets.

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Section: Resultsmentioning

confidence: 86%

Differentially Expressed Proteins in Malignant and Benign Adrenocortical Tumors

et al. 2014

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“…Importantly, we found that the expression levels of GRIM-19 and NDUFS3 were decreased level in the highly invasive breast cancer cell lines in comparison with that in the weakly invasive lines by screening of a panel of breast cancer cells (Figure 5), which support the role of mitochondrial complex I and even mitochondrial respiratory chain (RC) in the tumor cell invasion. In addition, decreased expression levels of GRIM-19 and NDUFS3 were found in renal cell carcinomas samples by western blot and RT-PCR analysis [16]–[17]. NDUFS3 was also reported to be decreased in breast cancer carcinoma [18].…”

Section: Discussionmentioning

confidence: 92%

Suppression of Mitochondrial Complex I Influences Cell Metastatic Properties

Zhou

et al. 2013

PLoS ONE

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Despite the fact that mitochondrial dysfunction has an important role in tumorigenesis and metastasis, the underlying mechanism remains to be elucidated. Mitochondrial Complex I (NADH:ubiquinone oxidoreductase) is the first and the largest protein complex of the mitochondrial electron-transport chain (ETC),which has an essential role in maintaining mitochondrial function and integrity. In this study, we separately knocked down two subunits of mitochondrial complex I, GRIM-19 or NDUFS3, and investigated their effects on metastatic behaviors and explored the possible mechanisms. Our data showed that stable down-modulation of GRIM-19 or NDUFS3 decreased complex I activity and reactive oxygen species (ROS) production; led to enhanced cell adhesion, migration, invasion, and spheroid formation; and influenced the expressions of extracellular matrix (ECM) molecules and its related proteins. We also observed that the expressions of GRIM-19, NDUFS3, and ECM elements were correlated with invasive capabilities of breast cancer cell lines. These results suggest that inhibition of complex I affects metastatic properties of cancer cells, and mitochondrial ROS might play a crucial role in these processes by regulating ECM.

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“…GRIM-19 functions as a tumor suppressor by inducing apoptosis (Tripathy and others 2010;Zhou and others 2011;Ekchariyawat and others 2013), inhibiting cell growth (Papa and others 2007;Zhang and others 2008;Okamoto and others 2010;Zhang and others 2011;Liu and others 2012) and blocking cell migration, invasion, and epithelial-mesenchymal transition (Huang and others 2010;Hao and others 2012). Consistent with its growth-suppressive properties, downregulation of GRIM-19 gene expression is commonly observed in human malignant tumors of the kidney (He and Cao 2010), breast (Zhou and others 2013;Zhang and others 2015), liver (Hao and others 2012), and lung (Fan and others 2012); and mutations in human GRIM-19 have been reported in Hürthle cell thyroid carcinomas and primary human head and neck cancers (Fusco and others 2005;Maximo and others 2005). Previously, we have reported that GRIM-19 is downregulated in cervical cancer and cervical squamous intraepithelial neoplasia (Zhou and others 2009;Cheng and others 2014) and demonstrated that restoring GRIM-19 expression can increase p53 protein levels and suppress the STAT3-mediated oncogenic signaling in cervical cancer others 2009, 2011).…”

Section: Introductionmentioning

confidence: 69%

GRIM-19 Restores Cervical Cancer Cell Senescence by Repressing hTERT Transcription

Ying

Feng

et al. 2016

Journal of Interferon & Cytokine Research

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High telomerase activity promotes tumor growth by stabilizing damaged chromosomes and their mitotic replication. Overactivation of telomerase activity has been reported in cervical cancer, a malignancy caused by high-risk human papillomaviruses (HR-HPVs). The HR-HPV E6 can activate hTERT promoter by interacting with E6AP or other binding proteins and by stabilizing the interaction between hTERT and E6AP. GRIM-19 is a novel tumor suppressor that affects multiple targets in a cell to regulate growth. We have previously reported the interaction of GRIM-19 with 18E6 and E6AP to disrupt the E6/E6AP complex and increase the autoubiquitination of E6AP. In this study, we characterized the interaction of GRIM-19 with 16E6 (an oncoprotein produced by HPV16) and identified the binding sites that mediate this interaction. We also found that GRIM-19 expression in cervical cancer cells could inhibit telomerase activity by inhibiting the transactivation of the hTERT promoter by E6, thereby promoting cervical cancer cell senescence. Moreover, we identified a negative correlation between GRIM-19 and hTERT expression in cervical cancer tissues. Suppression of GRIM-19 and induction of hTERT levels were associated with lymph node metastasis, advanced clinical stage, and poor prognosis. This study identified another important novel antitumor molecular link associated with GRIM-19 in the tumorigenesis.

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Identification of alternatively spliced GRIM-19 mRNA in kidney cancer tissues

Cited by 15 publications

References 27 publications

Differentially Expressed Proteins in Malignant and Benign Adrenocortical Tumors

Differentially Expressed Proteins in Malignant and Benign Adrenocortical Tumors

Suppression of Mitochondrial Complex I Influences Cell Metastatic Properties

GRIM-19 Restores Cervical Cancer Cell Senescence by Repressing hTERT Transcription

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