Preferential star strand biogenesis of pre-miR-24-2 targets PKC-alpha and suppresses cell survival in MCF-7 breast cancer cells.
microRNAs (miRNA) are regulators of cellular pathways and alterations of normal miRNA expression levels have been shown to increase tumorigenesis. miR-24 has been demonstrated as having both tumor suppressive and oncogenic properties depending on cell context. Here, we demonstrate a possible role for pre-miR-24-2 as a tumor suppressor in the MCF-7 breast cancer cell line through the preferential processing of mature miR-24-2* over miR-24. Specifically, we show that the ectopic expression of miR-24-2* in MCF-7 breast cancer cells results in a suppression of cellular survival both in vivo and in vitro. Notably, the overexpression of miR-24-2* results in a dampening of cell survival through the targeted suppression of PKCα. In addition, a similar biological change is observed in vivo where MCF-7 cells overexpressing pre-miR-24-2 have decreased tumorigenicity and tumor incidence. Taken together our data demonstrate that when overexpressed biogenesis of the pre-miR-24-2 favors miR-24-2* in the MCF-7 breast cancer cell line and suggests a tumor suppressive role for miR-24-2* observed through the inhibition of PKCα-mediated cellular survival.
Department of Medicine, Section of Hematology and Medical Oncology, Tulane University, New Orleans, Louisiaina.
Elizabeth C
EC
Martin
Steven
S
Elliott
Lyndsay V
LV
Rhodes
James W
JW
Antoon
Claire
C
Fewell
Yun
Y
Zhu
Jennifer L
JL
Driver
Mona
M
Jodari-Karimi
Christopher W
CW
Taylor
Erik K
EK
Flemington
Barbara S
BS
Beckman
Bridgette M
BM
Collins-Burow
Matthew E
ME
Burow
D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
D007527:Isoenzymes; C543845:MIRN24 microRNA, human; D035683:MicroRNAs; D051571:Protein Kinase C-alpha