title: CARM1 and PRMT1 are dysregulated in lung cancer without hierarchical features.
abstract: CARM1 and PRMT1 are 2 Protein Arginine Methyl Transferases (PRMT) dysregulated in cancer. CARM1 function is contradictory and depicted as facilitating proliferation or differentiation. PRMT1 is required for cell proliferation. CARM1 and PRMT1 cooperate for gene regulation. We report that CARM1 and PRMT1 are significantly overexpressed in 60 patients with Non-Small Cell Lung Carcinomas (NSCLC). CARM1 and PRMT1 correlated in healthy but not tumor tissue. Their levels of expression in tumor tissue were proportional to their levels of expression in the counterpart healthy tissue. Only CARM1 expression was found to be correlated with tumor differentiation and neither CARM1 nor PRMT1 expression was correlated with survival. Accordingly, CARM1 and PRMT1 are overexpressed in 2 NSCLC cell lines, A549 and H1299. Targeting PRMT1 with siRNA reduced proliferation, by decreasing cell growth and inhibiting soft agar colony formation, and promoted differentiation, by increasing the epithelial markers cytokeratin 7 and 8 and decreasing Neuromedin B receptor, which binds a mitogenic factor. siCARM1 yielded similar consequences but the conditions with siCARM1 reflected inhibition of both CARM1 and PRMT1. Together these results suggest that CARM1 and PRMT1 are involved in proliferation in lung cancer with no hierarchy of one protein over the other. The fact that CARM1 targeting suppresses PRMT1 in addition to CARM1 reinforces the functional importance of CARM1/PRMT1 interaction.
authors.affiliation: INSERM NGERE UMR 954, Vandoeuvre F-54500, France.
authors.forename: Rania
authors.initials: R
authors.lastname: Elakoum
authors.affiliation: INSERM NGERE UMR 954, Vandoeuvre F-54500, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gauchotte
authors.affiliation: INSERM NGERE UMR 954, Vandoeuvre F-54500, France.
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Oussalah
authors.affiliation: INSERM NGERE UMR 954, Vandoeuvre F-54500, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Wissler
authors.affiliation: INSERM NGERE UMR 954, Vandoeuvre F-54500, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Clément-Duchêne
authors.affiliation: INSERM NGERE UMR 954, Vandoeuvre F-54500, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vignaud
authors.affiliation: INSERM NGERE UMR 954, Vandoeuvre F-54500, France. Electronic address: jean-louis.gueant@univ-lorraine.fr.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guéant
authors.affiliation: INSERM NGERE UMR 954, Vandoeuvre F-54500, France. Electronic address: bernard.namour@univ-lorraine.fr.
authors.forename: Farès
authors.initials: F
authors.lastname: Namour
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053552:Keratin-7 / Q000235:genetics / Q000378:metabolism; D053533:Keratin-8 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018004:Receptors, Bombesin / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D053552:Keratin-7; D053533:Keratin-8; D034741:RNA, Small Interfering; D018004:Receptors, Bombesin; D012097:Repressor Proteins; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1
keywords: CARM1; Lung cancer; PRMT1; Proliferation; siRNA