CARM1 and PRMT1 are dysregulated in lung cancer without hierarchical features

Elakoum, Rania; Gauchotte, Guillaume; Oussalah, Abderrahim; Wissler, Marie-Pierre; Clément-Duchêne, Christelle; Vignaud, Jean-Michel; Guéant, Jean‐Louis; Namour, Farès

doi:10.1016/j.biochi.2013.10.021

Cited by 69 publications

(66 citation statements)

References 28 publications

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“…From the data in the present report and previous reports, PRMT1 is known to have a dual function as a tumor suppressor and promoter [15,17,19]. PRMT1 suppression may both induce antitumor effects and proliferation depending on the cell type.…”

Section: Discussionsupporting

confidence: 72%

“…Moreover, some studies reported that PRMT1 was associated with the inhibition of proliferation and apoptosis induction in lung cancer and gliomas [15,16]. On the other hand, PRMT1 inhibition was reported to induce suppression of the proliferation potency of bladder and lung cancer cells [17] and enhanced chemosensitivity via inhibition of DNA repair in osteosarcoma cells [18].…”

Section: Introductionmentioning

confidence: 99%

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Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients

et al. 2015

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Background Metastatic and refractory gastric cancer (GC) are associated with a poor prognosis; therefore, the identification of prognostic factors and chemosensitivity markers is extremely important. Protein arginine methyltransferase 1 (PRMT1) may play a role in chemosensitivity/apoptosis induction via activation of the tumor suppressor forkhead box O1 (FOXO1). The purpose of this study was to clarify the expression of and relationship between PRMT1 and FOXO1 to evaluate the applicability of PRMT1 as a prognostic marker and a therapeutic tool in GC. Methods We investigated the clinical and functional significance of PRMT1 and FOXO1 in 195 clinical GC samples using immunohistochemistry. We performed suppression analysis of PRMT1 using small interfering RNA to determine the biological roles of PRMT1 in chemosensitivity. Results PRMT1 and FOXO1 in GC samples were predominantly expressed in the nucleus. Patients with lower PRMT1 expression (n = 131) had suppressed nuclear accumulation of FOXO1, higher recurrence after adjuvant chemotherapy, and poorer prognosis than those with higher PRMT1 expression (n = 64). PRMT1 downregulation in GC cells by RNA interference inhibited cisplatin and 5-fluorouracil sensitivity. The expression of phosphorylated FOXO1 and phosphorylated BCL-2 antagonist of cell death was upregulated in PRMT1 small interfering RNA groups. Conclusion Our data suggest that the evaluation of PRMT1 expression in GC is a useful predictor of poor prognosis and recurrence after adjuvant chemotherapy. Moreover, these data suggest that PRMT1 is a promising therapeutic tool for overcoming refractory GC.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients

et al. 2015

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“…Primary antibodies used in immunocytochemistry were raised against FEN1. Immunoreactivities were analyzed by estimating the percentage of cells showing characteristic staining and the intensity of staining (Elakoum et al, 2014). The intensity of staining was graded as 1 (weak), 2 (medium), or 3 (strong).…”

Section: Methodsmentioning

confidence: 99%

Targeting DNA Flap Endonuclease 1 to Impede Breast Cancer Progression

Zhang

Sun

et al. 2016

EBioMedicine

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DNA flap endonuclease 1 (FEN1) plays critical roles in maintaining genome stability and integrity by participating in both DNA replication and repair. Suppression of FEN1 in cells leads to the retardation of DNA replication and accumulation of unrepaired DNA intermediates, resulting in DNA double strand breaks (DSBs) and apoptosis. Therefore, targeting FEN1 could serve as a potent strategy for cancer therapy. In this study, we demonstrated that FEN1 is overexpressed in breast cancers and is essential for rapid proliferation of cancer cells. We showed that manipulating FEN1 levels in cells alters the response of cancer cells to chemotherapeutic drugs. Furthermore, we identified a small molecular compound, SC13 that specifically inhibits FEN1 activity, thereby interfering with DNA replication and repair in vitro and in cells. SC13 suppresses cancer cell proliferation and induces chromosome instability and cytotoxicity in cells. Importantly, SC13 sensitizes cancer cells to DNA damage-inducing therapeutic modalities and impedes cancer progression in a mouse model. These findings could establish a paradigm for the treatment of breast cancer and other cancers as well.

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“…CARM1 is involved in the initiation and progression of various human tumors. Based on the previous studies, abnormal expression of CARM1, mostly upregulation, is associated with human prostate, 10,11 breast, 7 lung, 17 and colorectal cancers. 18 Although levels of CARM1 have been reported to correlate with some cancers, the roles of CARM1 are controversial and seem to be context dependent.…”

Section: Discussionmentioning

confidence: 96%

Coactivator-associated arginine methyltransferase 1 promotes cell growth and is targeted by microRNA-195-5p in human colorectal cancer

Zhang

Gao

et al. 2017

Tumour Biol.

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The pathogenesis of colorectal cancer remains poorly understood. Here, we show that coactivator-associated arginine methyltransferase 1 is frequently upregulated in colorectal cancer tissues and promotes cell growth in vitro and in vivo. Using bioinformatics-based prediction and luciferase reporter system, we found that coactivatorassociated arginine methyltransferase 1 is post-transcriptionally targeted by microRNA-195-5p in colorectal cancer. Ectopic expression of microRNA-195-5p led to the suppression of the coactivator-associated arginine methyltransferase 1 3′-untranslated regions activity and downregulation of the endogenous coactivator-associated arginine methyltransferase 1 protein in colorectal cancer cells. Expression analysis verified that microRNA-195-5p was markedly downregulated in human colorectal cancer tissues, which was negatively correlated with the elevated levels of coactivator-associated arginine methyltransferase 1 protein. Enhanced levels of microRNA-195-5p in colorectal cancer cells resulted in a sharp reduction of cell proliferative and colony-formative capacities in vitro. Remarkably, restoration of coactivator-associated arginine methyltransferase 1 in microRNA-195-5p-transfected colorectal cancer cells partially abrogated the inhibition of cell proliferation and colony formation mediated through microRNA-195-5p. These data confirm that microRNA-195-5p might function as an anti-tumor microRNA in colorectal cancer exerting critical control over coactivator-associated arginine methyltransferase 1 expression. The newly identified microRNA-195-5p/coactivator-associated arginine methyltransferase 1 axis may act as a novel promising therapeutic target for colorectal cancer treatment.

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CARM1 and PRMT1 are dysregulated in lung cancer without hierarchical features

Cited by 69 publications

References 28 publications

Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients

Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients

Targeting DNA Flap Endonuclease 1 to Impede Breast Cancer Progression

Coactivator-associated arginine methyltransferase 1 promotes cell growth and is targeted by microRNA-195-5p in human colorectal cancer

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