Identification of a Novel Tumor Suppressor Gene <i>p34</i> on Human Chromosome 6q25.1

Wang, Min; Vikis, Haris G.; Wang, Yian; Jia, Dongmei; Wang, Daolong; Bierut, Laura J.; Bailey-Wilson, Joan E.; Amos, Christopher I.; Pinney, Susan M.; Petersen, Gloria M.; Andrade, Mariza de; Yang, Ping; Wiest, Jonathan S.; Fain, Pamela R.; Schwartz, Ann G.; Gazdar, Adi F.; Minna, John D.; Gaba, Colette; Rothschild, Henry; Mandal, Diptasri; Kupert, Elena; Seminara, Daniela; Liu, Yan; Viswanathan, Avinash; Govindan, Ramaswamy; Anderson, Marshall W.; You, Ming

doi:10.1158/0008-5472.can-06-2723

Cited by 40 publications

(48 citation statements)

References 18 publications

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“…The high frequency for LOH and the potential existence of a susceptibility locus within 6q23-25 supports the existence of tumor suppressor genes inactivated through the classic Knudson's two-hit model in which complete loss of gene function arises through loss of one allele and mutation of the second allele (11). However, only one candidate tumor suppressor gene, p34, localized to 6q25 has been identified, but this gene was not found to be associated with familial lung cancer susceptibility (12). This scenario is reminiscent of the chromosome 3p14-25 in which LOH is commonly seen in lung tumors, although no major tumor suppressor gene inactivated by mutation has been identified in this locus.…”

Section: Introductionmentioning

confidence: 94%

Promoter Methylation of Genes in and around the Candidate Lung Cancer Susceptibility Locus 6q23-25

et al. 2008

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Chromosomal aberrations associated with lung cancer are frequently observed in the long arm of chromosome 6. A candidate susceptibility locus at 6q23-25 for lung cancer was recently identified; however, no tumor suppressor genes inactivated by mutation have been identified in this locus. Genetic, epigenetic, gene expression, and in silico screening approaches were used to select 43 genes located in 6q12-27 for characterization of methylation status. Twelve (28%) genes were methylated in at least one lung cancer cell line, and methylation of 8 genes was specific to lung cancer cell lines. Five of the 8 genes with the highest prevalence for methylation in cell lines (TCF21, SYNE1, AKAP12, IL20RA, and ACAT2) were examined in primary lung adenocarcinoma samples from smokers (n = 100) and never smokers (n = 75). The prevalence for methylation of these genes was 81%, 50%, 39%, 26%, and 14%, respectively, and did not differ by smoking status or age at diagnosis. Transcription of SYNE1, AKAP12, and IL20RA was completely silenced by hypermethylation and could be restored after treatment with 5-aza-2-deoxycytidine. Significant associations were found between methylation of SYNE1 and TCF21, SYNE1 and AKAP12, and AKAP12 and IL20RA, indicating a coordinated inactivation of these genes in tumors. A higher prevalence for methylation of these genes was not associated with early-onset lung cancer cases, most likely precluding their involvement in familial susceptibility to this disease. Together, our results indicate that frequent inactivation of multiple candidate tumor suppressor genes within chromosome 6q likely contributes to development of sporadic lung cancer.

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Section: Introductionmentioning

confidence: 94%

Promoter Methylation of Genes in and around the Candidate Lung Cancer Susceptibility Locus 6q23-25

et al. 2008

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“…TFL has a conserved RNA-binding CCCH-type zinc finger domain and an A/G nonsynonymous SNP at codon 106, which has been shown to exert tumor suppressor function (19). Therefore, these mutants could affect cell proliferation.…”

Section: Noninterference Of Tfl With the Static State Of Immunitymentioning

confidence: 99%

“…TFL has a single CCCH-type zinc finger motif and is a member of the Zc3h12 family (18). TFL was also identified as the novel tumor suppressor gene p34 in lung cancer loss of heterozygosity research (19); however, the dominant endogenous TFL was later revealed as 58 kDa (20). Whereas TFL expresses several leukemic cell lines, including HL-60, THP-1, HUT102, Daudi, and Nalm-6, some T cell leukemic cell lines, including Jurkat, MOLT-14, and CCRF/CEM, do not express TFL.…”

mentioning

confidence: 99%

Posttranscriptional Modulation of Cytokine Production in T Cells for the Regulation of Excessive Inflammation by TFL

Minagawa

Wakahashi

Kawano

et al. 2014

The Journal of Immunology

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Posttranscriptional machinery regulates inflammation and is associated with autoimmunity as well as tumorigenesis in collaboration with transcription factors. We previously identified the tumor suppressor gene transformed follicular lymphoma (TFL) on 6q25 in a patient with follicular lymphoma, which transformed into diffuse large B cell lymphoma. TFL families have a common RNase domain that governs macrophage-mediated inflammation. In human peripheral blood, TFL is dominantly expressed at the glycine- and tryptophan-rich cytoplasmic processing bodies of T lymphocytes, and it is persistently upregulated in activated T cells. To address its physiological role, we established TFL−/− mice in which TFL−/− lymphocytes proliferated more rapidly than TFL+/+ upon stimulation with inappropriate cytokine secretion, including IL-2, IL-6, and IL-10. Moreover, TFL inhibited the synthesis of cytokines such as IL-2, IL-6, IL-10, TNF-α, and IL-17a by 3′ untranslated region RNA degradation. Experimental autoimmune encephalitis induced in TFL−/− mice demonstrated persistent severe paralysis. CNS-infiltrated CD4+ T cells in TFL−/− mice contained a higher proportion of Th17 cells than did those in TFL+/+ mice during the resolution phase, and IL-17a mRNA levels were markedly increased in TFL−/− cells. These results suggest that TFL may play an important role in attenuating local inflammation by suppressing the infiltration of Th17 cells in the CNS during the resolution phase of experimental autoimmune encephalitis. TFL is a novel gradual and persistent posttranscriptional regulator, and the TFL-driven attenuation of excessive inflammation could contribute to recovery from T cell–mediated autoimmune diseases.

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“…MCPIP4 (also known as ZC3H12D, TFL, and p34) was originally reported as a putative tumor suppressor that is deregu-lated in transformed follicular lymphoma (17)(18)(19). Similar to MCPIP1, MCPIP4 is also remarkably induced by Toll-like receptor activation in macrophages and overexpression of MCPIP4 also represses inflammatory activation of macrophages (20).…”

mentioning

confidence: 99%

Monocyte Chemotactic Protein-induced Protein 1 and 4 Form a Complex but Act Independently in Regulation of Interleukin-6 mRNA Degradation

Huang

et al. 2015

Journal of Biological Chemistry

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It was recently demonstrated that MCPIP1 is a critical factor that controls inflammation and immune homeostasis; however, the relationship between MCPIP1 and other members of this protein family is largely unknown. Here, we report that MCPIP1 interacts with MCPIP4 to form a protein complex, but acts independently in the regulation of IL-6 mRNA degradation. In an effort to identify MCPIP1-interacting proteins by co-immunoprecipitation (Co-IP) and mass-spec analysis, MCPIP4 was identified as a MCPIP1-interacting protein, which was further confirmed by Co-IP and mammalian two-hybrid assay. Immunofluorescence staining showed that MCPIP4 was co-localized with MCPIP1 in the GW-body, which features GW182 and Argonaute 2. Further studies showed that MCPIP1 and MCPIP4 act independently in regulation of IL-6 mRNA degradation. These results suggest that MCPIP1 and MCPIP4 may additively contribute to control IL-6 production in vivo.

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Identification of a Novel Tumor Suppressor Gene p34 on Human Chromosome 6q25.1

Cited by 40 publications

References 18 publications

Promoter Methylation of Genes in and around the Candidate Lung Cancer Susceptibility Locus 6q23-25

Promoter Methylation of Genes in and around the Candidate Lung Cancer Susceptibility Locus 6q23-25

Posttranscriptional Modulation of Cytokine Production in T Cells for the Regulation of Excessive Inflammation by TFL

Monocyte Chemotactic Protein-induced Protein 1 and 4 Form a Complex but Act Independently in Regulation of Interleukin-6 mRNA Degradation

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