p53-Mediated Activation of miRNA34 Candidate Tumor-Suppressor Genes

Bommer, Guido T.; Gerin, Isabelle; Feng, Ying; Kaczorowski, Andrew J.; Kuick, Rork; Love, Robert F.; Zhai, Yali; Giordano, Thomas J.; Qin, Zhaohui S.; Moore, Bethany B.; MacDougald, Ormond A.; Cho, Kathleen R.; Fearon, Eric R.

doi:10.1016/j.cub.2007.06.068

Cited by 1,010 publications

(996 citation statements)

References 34 publications

(40 reference statements)

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“…In general, our findings strongly support the existing literature that Axl is an oncogene and miR-34a is a tumor suppressor (Hafizi and Dahlback, 2006;Vajkoczy et al, 2006;Bommer et al, 2007;Welch et al, 2007;Mudduluru et al, 2010). Previous studies reported that miR-34a can inhibit cell cycle (CCNE2, CDK4, CDK6, Cyclin E2 and E2F5), anti-apoptotic protein (BCL2) and invasion (MET) inducing genes (Bommer et al, 2007;Chang et al, 2007;He et al, 2007;Raver-Shapira et al, 2007). Additionally, 199a and 199b can inhibit cell proliferation by targeting cell proliferation inducers like IKKb, HES1, Cyclin D1 and C-Myc (Chen et al, 2008;Garzia et al, 2009).…”

Section: Discussionsupporting

confidence: 91%

“…Axl-mRNA and Axl protein expression significantly inversely correlated with the miR-34a expression, and cell invading capacity positively correlated with Axl protein amounts and inversely with miR-34a expression. In general, our findings strongly support the existing literature that Axl is an oncogene and miR-34a is a tumor suppressor (Hafizi and Dahlback, 2006;Vajkoczy et al, 2006;Bommer et al, 2007;Welch et al, 2007;Mudduluru et al, 2010). Previous studies reported that miR-34a can inhibit cell cycle (CCNE2, CDK4, CDK6, Cyclin E2 and E2F5), anti-apoptotic protein (BCL2) and invasion (MET) inducing genes (Bommer et al, 2007;Chang et al, 2007;He et al, 2007;Raver-Shapira et al, 2007).…”

Section: Discussionsupporting

confidence: 91%

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Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer

et al. 2011

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Axl is a receptor that induces proliferation, migration and invasion in cancer. In this study, we show that specific microRNAs (miRNAs) target the 3 0 -UTR of Axl. Luciferase-reporter assays with wild-type and deleted miR-34 and miR-199a/b seed sequences of Axl 3 0 -UTR confirmed the specificity of targeting. An inverse correlation between Axl protein and miR-34a expression in a panel of non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and breast cancer (BRC) cell lines was observed, while miR-199a/b expression was completely suppressed. Pre-miR transfection inhibited in vitro migration and invasion and, in vivo, reduced the number of distant lung-or liver-metastases in a chorion-allantoicmembrane (CAM) assay. Moreover, methylation-specific PCR on bisulfite-converted DNA obtained from the cell lines showed that the miR-34a promoter methylation status was inversely correlated with its expression, and that miR-199a/b promoter regions were methylated in all cells tested. In a panel of NSCLC tissues (n ¼ 44), miR34a and miR-199a/b were found to be downregulated and significantly co-expressed. A lower expression of all three miRs was significantly associated with squamous histotypes, and, in a preliminary series, NSCLC patients with miR-34a upregulation showed a positive association towards a longer survival. These results indicate that Axl receptor expression can be regulated by miR-34a and miR-199a/b, which are suppressed by promoter methylation in solid cancer cells.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer

et al. 2011

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“…MiR-34 family, which is composed of miR-34a, miR-34b and miR-34c, modulates cell cycle progression, senescence and apoptosis [6,21,22]. MiR-34a is highly expressed in normal tissues, like testis, lung, adrenal gland and spleen.…”

Section: Discussionmentioning

confidence: 99%

TBHP-induced oxidative stress alters microRNAs expression in mouse testis

Fatemi

Sanati

Shamsara

et al. 2014

J Assist Reprod Genet

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Purpose Reactive oxygen species (ROS) and oxidative stress is one of the main reasons of male infertility. MicroRNAs (miRNAs) regulate multiple intracellular processes. Alterations in miRNAs expression may occur in different conditions and diseases. In this study, the effect of oxidative stress induced by tertiary-butyl hydroperoxide (TBHP) on the expression of candidate miRNAs in mouse testis was investigated.Methods After determining median lethal dose (LD 50 ), TBHP was intraperitoneally (ip) injected at the dilution of 1:10 LD 50 into the adult male mice for 2weeks, and then testis tissues were removed in order to assay the ROS level. Total RNA was extracted and the expression of five miRNAs was quantified by reverse transcription-real time polymerase chain reaction (RT-qPCR).Results The flow cytometry analysis showed a significant increase in ROS level in testis. The expression of three out of five selected miRNAs, including miR-34a, miR-181b and miR-122a, showed some degrees of changes following exposure to oxidative stress. These miRNAs are involved in antioxidant responses, inflammation pathway and spermatogenesis arrest. Conclusions In conclusion, TBHP alters the miRNA expression profile of testis which might play a potential role in oxidative and antioxidative responses and spermatogenesis.

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“…Both are targeted by miR-29 and miR-153, [72][73][74] and BCL-2 expression is also regulated by miR-15, miR-16, 75 miR-195 76 and the p53-inducible miR-34. 77 BCL-XL expression appears to be controlled by miR-491. 78 Role of the BCL-2-Regulated Apoptotic Pathway in Mouse Models of Tumorigenesis Experimental models have been utilised to delineate the roles of the various BCL-2 family proteins during tumorigenesis ( Table 1).…”

Section: Mcl1mentioning

confidence: 99%

The BCL-2 protein family, BH3-mimetics and cancer therapy

2015

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Escape from apoptosis is a key attribute of tumour cells and facilitates chemo-resistance. The 'BCL-2-regulated' or 'intrinsic' apoptotic pathway integrates stress and survival signalling to govern whether a cancer cell will live or die. Indeed, many pro-apoptotic members of the BCL-2 family have demonstrated tumour-suppression activity in mouse models of cancer and are lost or repressed in certain human cancers. Conversely, overexpression of pro-survival BCL-2 family members promotes tumorigenesis in humans and in mouse models. Many of the drugs currently used in the clinic mediate their therapeutic effects (at least in part) through the activation of the BCL-2-regulated apoptotic pathway. However, initiators of this apoptotic pathway, such as p53, are mutated, lost or silenced in many human cancers rendering them refractory to treatment. To counter such resistance mechanisms, a novel class of therapeutics, 'BH3-mimetics', has been developed. These drugs directly activate apoptosis by binding and inhibiting select antiapoptotic BCL-2 family members and thereby bypass the requirement for upstream initiators, such as p53. In this review, we discuss the role of the BCL-2 protein family in the development and treatment of cancer, with an emphasis on mechanistic studies using well-established mouse models of cancer, before describing the development and already recognised potential of the BH3-mimetic compounds.

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p53-Mediated Activation of miRNA34 Candidate Tumor-Suppressor Genes

Abstract: Taken together, the data suggest the miRNA34s might be key effectors of p53 tumor-suppressor function, and their inactivation might contribute to certain cancers.

Cited by 1,010 publications

References 34 publications

Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer

Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer

TBHP-induced oxidative stress alters microRNAs expression in mouse testis

The BCL-2 protein family, BH3-mimetics and cancer therapy

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