We are analyzing https://link.springer.com/article/10.1186/s11658-023-00487-0.

Title:
MCCC2 is a novel mediator between mitochondria and telomere and functions as an oncogene in colorectal cancer | Cellular & Molecular Biology Letters
Description:
Background The mitochondrial gene MCCC2, a subunit of the heterodimer of 3-methylcrotonyl-CoA carboxylase, plays a pivotal role in catabolism of leucine and isovaleric acid. The molecular mechanisms and prognostic value still need to be explored in the context of specific cancers, including colorectal cancer (CRC). Methods In vitro and in vivo cell-based assays were performed to explore the role of MCCC2 in CRC cell proliferation, invasion, and migration. Mitochondrial morphology, membrane potential, intracellular reactive oxygen species (ROS), telomerase activity, and telomere length were examined and analyzed accordingly. Protein complex formation was detected by co-immunoprecipitation (CO-IP). Mitochondrial morphology was observed by transmission electron microscopy (TEM). The Cancer Genome Atlas (TCGA) CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the MCCC2 expression level. The association between MCCC2 expression and various clinical characteristics was analyzed by chi-square tests. CRC patients’ overall survival (OS) was analyzed by Kaplan–Meier analysis. Results Ectopic overexpression of MCCC2 promoted cell proliferation, invasion, and migration, while MCCC2 knockdown (KD) or knockout (KO) inhibited cell proliferation, invasion, and migration. MCCC2 KD or KO resulted in reduced mitochondria numbers, but did not affect the gross ATP production in the cells. Mitochondrial fusion markers MFN1, MFN2, and OPA1 were all upregulated in MCCC2 KD or KO cells, which is in line with a phenomenon of more prominent mitochondrial fusion. Interestingly, telomere lengths of MCCC2 KD or KO cells were reduced more than control cells. Furthermore, we found that MCCC2 could specifically form a complex with telomere binding protein TRF2, and MCCC2 KD or KO did not affect the expression or activity of telomerase reverse transcriptase (TERT). Finally, MCCC2 expression was heightened in CRC, and patients with higher MCCC2 expression had favorable prognosis. Conclusions Together, we identified MCCC2 as a novel mediator between mitochondria and telomeres, and provided an additional biomarker for CRC stratification.
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mccc, cells, cell, mitochondrial, pubmed, crc, cancer, fig, expression, google, scholar, telomere, cas, trf, mitochondria, tumor, proliferation, showed, patients, protein, telomerase, analysis, ros, fusion, tissues, assay, colorectal, central, data, cat, invasion, mfn, complex, level, control, deficiency, cellular, tert, levels, oemccc, ihc, calculate, chen, migration, activity, telomeres, study, usa, mrna, overexpression,

Topics {✒️}

3-methylcrotonyl-coa carboxylase deficiency real-time cell analyzer mitochondrial methylcrotonoyl-coa carboxylase ap-mn-ms-gdna-4 acyl-coa binding region sun yat-sen university article download pdf 3-methylcrotonyl-coa carboxylase rna-quick purification kit oxidation-sensitive fluorescent probe induce single-strand breaks isolate single-cell clones flag-tagged full-length colorectal cancer metastases view underlying molecular basics full access vivo cell-based assays including colorectal cancer individual round-shaped mitochondria drives telomere-dependent disease colorectal cancer statistics colorectal cancer immunotherapy chemokine ligand c-x daici chen metastatic colorectal cancer cancer genome atlas fbs-free culture medium thermo fisher scientific mitochondria-specific fluorescence probe promotes cell proliferation kaplan–meier survival curves reactive oxygen species 10 µm dcfh-da dissolved maintains mitochondrial homogeneity laboratory animal center inhibited cell proliferation mccc2 promotes proliferation tcga-crc cohort analysis mitochondrial fusion–fission dynamics flag-mccc2 overexpressing plasmid privacy choices/manage cookies human chromosome end quantitative interaction screen search decreased cellular respiration regulating telomerase recruitment original author cancer biology crispr/cas9 system

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         headline:MCCC2 is a novel mediator between mitochondria and telomere and functions as an oncogene in colorectal cancer
         description:The mitochondrial gene MCCC2, a subunit of the heterodimer of 3-methylcrotonyl-CoA carboxylase, plays a pivotal role in catabolism of leucine and isovaleric acid. The molecular mechanisms and prognostic value still need to be explored in the context of specific cancers, including colorectal cancer (CRC). In vitro and in vivo cell-based assays were performed to explore the role of MCCC2 in CRC cell proliferation, invasion, and migration. Mitochondrial morphology, membrane potential, intracellular reactive oxygen species (ROS), telomerase activity, and telomere length were examined and analyzed accordingly. Protein complex formation was detected by co-immunoprecipitation (CO-IP). Mitochondrial morphology was observed by transmission electron microscopy (TEM). The Cancer Genome Atlas (TCGA) CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the MCCC2 expression level. The association between MCCC2 expression and various clinical characteristics was analyzed by chi-square tests. CRC patients’ overall survival (OS) was analyzed by Kaplan–Meier analysis. Ectopic overexpression of MCCC2 promoted cell proliferation, invasion, and migration, while MCCC2 knockdown (KD) or knockout (KO) inhibited cell proliferation, invasion, and migration. MCCC2 KD or KO resulted in reduced mitochondria numbers, but did not affect the gross ATP production in the cells. Mitochondrial fusion markers MFN1, MFN2, and OPA1 were all upregulated in MCCC2 KD or KO cells, which is in line with a phenomenon of more prominent mitochondrial fusion. Interestingly, telomere lengths of MCCC2 KD or KO cells were reduced more than control cells. Furthermore, we found that MCCC2 could specifically form a complex with telomere binding protein TRF2, and MCCC2 KD or KO did not affect the expression or activity of telomerase reverse transcriptase (TERT). Finally, MCCC2 expression was heightened in CRC, and patients with higher MCCC2 expression had favorable prognosis. Together, we identified MCCC2 as a novel mediator between mitochondria and telomeres, and provided an additional biomarker for CRC stratification.
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            Mitochondria
            Telomere
            Colorectal cancer
            Cell Biology
            Biochemistry
            general
            Biological and Medical Physics
            Biophysics
            Biotechnology
            Molecular Medicine
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         Mitochondria
         Telomere
         Colorectal cancer
         Cell Biology
         Biochemistry
         general
         Biological and Medical Physics
         Biophysics
         Biotechnology
         Molecular Medicine
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               name:Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
               type:PostalAddress
            type:Organization
            name:The Sixth Affiliated Hospital, Sun Yat-sen University
            address:
               name:Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Department of Intensive Care Unit, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Department of Intensive Care Unit, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Scientific Journal Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

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