title: Calcitriol increases Dicer expression and modifies the microRNAs signature in SiHa cervical cancer cells.
abstract: MicroRNAs play important roles in cancer biology. Calcitriol, the hormonal form of vitamin D3, regulates microRNAs expression in tumor cells. In the present study we asked if calcitriol would modify some of the components of the microRNA processing machinery, namely, Drosha and Dicer, in calcitriol-responsive cervical cancer cells. We found that calcitriol treatment did not affect Drosha mRNA; however, it significantly increased Dicer mRNA and protein expression in VDR-positive SiHa and HeLa cells. In VDR-negative C33-A cells, calcitriol had no effect on Dicer mRNA. We also found a vitamin D response element in Dicer promoter that interacts in vitro to vitamin D and retinoid X receptors. To explore the biological plausibility of these results, we asked if calcitriol alters the microRNA expression profile in SiHa cells. Our results revealed that calcitriol regulates the expression of a subset of microRNAs with potential regulatory functions in cancer pathways, such as miR-22, miR-296-3p, and miR-498, which exert tumor-suppressive effects. In summary, the data indicate that in SiHa cells, calcitriol stimulates the expression of Dicer possibly through the vitamin D response element located in its promoter. This may explain the calcitriol-dependent modulation of microRNAs whose target mRNAs are related to anticancer pathways, further adding to the various anticancer mechanisms of calcitriol.
authors.affiliation: a Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga # 15, Col. Sección XVI, México, D.F. 14000, México.|e School of Medicine, Universidad Nacional Autónoma de México, Circuito Interior, Ciudad Universitaria, Av. Universidad # 3000, México, D.F. 04510, México.
authors.forename: Ramiro José
authors.initials: RJ
authors.lastname: González-Duarte
authors.affiliation: a Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga # 15, Col. Sección XVI, México, D.F. 14000, México.|e School of Medicine, Universidad Nacional Autónoma de México, Circuito Interior, Ciudad Universitaria, Av. Universidad # 3000, México, D.F. 04510, México.
authors.forename: Verna
authors.initials: V
authors.lastname: Cázares-Ordoñez
authors.affiliation: b Laboratory of Cancer Genomics, Instituto Nacional de Medicina Genómica, Periférico Sur # 4809, Col. Arenal Tepepan, México, D.F. 14610, México.
authors.forename: Sandra
authors.initials: S
authors.lastname: Romero-Córdoba
authors.affiliation: a Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga # 15, Col. Sección XVI, México, D.F. 14000, México.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Díaz
authors.affiliation: c Department of Physiology of Nutrition, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga # 15, Col. Sección XVI, México, D.F. 14000, México.
authors.forename: Víctor
authors.initials: V
authors.lastname: Ortíz
authors.affiliation: d Evolutionary Genomics Program, Center for Genomic Sciences, Universidad Nacional Autónoma de México, Av. Universidad s/n, Col. Chamilpa, Cuernavaca, Morelos 62210, México.
authors.forename: Julio Augusto
authors.initials: JA
authors.lastname: Freyre-González
authors.affiliation: b Laboratory of Cancer Genomics, Instituto Nacional de Medicina Genómica, Periférico Sur # 4809, Col. Arenal Tepepan, México, D.F. 14610, México.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Hidalgo-Miranda
authors.affiliation: a Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga # 15, Col. Sección XVI, México, D.F. 14000, México.
authors.forename: Fernando
authors.initials: F
authors.lastname: Larrea
authors.affiliation: a Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga # 15, Col. Sección XVI, México, D.F. 14000, México.
authors.forename: Euclides
authors.initials: E
authors.lastname: Avila
mesh_terms: D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic; D018167:Receptors, Calcitriol / Q000378:metabolism; D047488:Retinoid X Receptors / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*
chemical_list: D035683:MicroRNAs; D018167:Receptors, Calcitriol; D047488:Retinoid X Receptors; D043244:Ribonuclease III; D002117:Calcitriol
keywords: Dicer; Drosha; VDR; cancer cervical; cervical cancer; microARN; microRNA; vitamin D; vitamine D