LAMA4-Regulating miR-4274 and Its Host Gene SORCS2 Play a Role in IGFBP6-Dependent Effects on Phenotype of Basal-Like Breast Cancer
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LAMA4-Regulating miR-4274 and Its Host Gene SORCS2 Play a Role in IGFBP6-Dependent Effects on Phenotype of Basal-Like Breast Cancer. / Shkurnikov, Maxim; Nikulin, Sergey; Nersisyan, Stepan; Poloznikov, Andrey; Zaidi, Shan; Baranova, Ancha; Schumacher, Udo; Wicklein, Daniel; Tonevitsky, Alexander.
In: FRONT MOL BIOSCI, Vol. 6, 2019, p. 122.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - LAMA4-Regulating miR-4274 and Its Host Gene SORCS2 Play a Role in IGFBP6-Dependent Effects on Phenotype of Basal-Like Breast Cancer
AU - Shkurnikov, Maxim
AU - Nikulin, Sergey
AU - Nersisyan, Stepan
AU - Poloznikov, Andrey
AU - Zaidi, Shan
AU - Baranova, Ancha
AU - Schumacher, Udo
AU - Wicklein, Daniel
AU - Tonevitsky, Alexander
N1 - Copyright © 2019 Shkurnikov, Nikulin, Nersisyan, Poloznikov, Zaidi, Baranova, Schumacher, Wicklein and Tonevitsky.
PY - 2019
Y1 - 2019
N2 - Specificity of RNAi to selected target is challenged by off-target effects, both canonical and non-canonical. Notably, more than half of all human microRNAs are co-expressed with hosting them proteincoding genes. Here we dissect regulatory subnetwork centered on IGFBP6 gene, which is associated with low proliferative state and high migratory activity of basal-like breast cancer. We inhibited expression of IGFBP6 gene in a model cell line for basal-like breast carcinoma MDA-MB-231, then traced secondary and tertiary effects of this knockdown to LAMA4, a laminin encoding gene that contributes to the phenotype of triple-negative breast cancer. LAMA4-regulating miRNA miR-4274 and its host gene SORCS2 were highlighted as intermediate regulators of the expression levels of LAMA4, which correlated in a basal-like breast carcinoma sample subset of TCGA to the levels of SORCS2 negatively. Overall, our study points that the secondary and tertiary layers of regulatory interactions are certainly underappreciated. As these types of molecular event may significantly contribute to the formation of the cell phenotypes after RNA interference based knockdowns, further studies of multilayered molecular networks affected by RNAi are warranted.
AB - Specificity of RNAi to selected target is challenged by off-target effects, both canonical and non-canonical. Notably, more than half of all human microRNAs are co-expressed with hosting them proteincoding genes. Here we dissect regulatory subnetwork centered on IGFBP6 gene, which is associated with low proliferative state and high migratory activity of basal-like breast cancer. We inhibited expression of IGFBP6 gene in a model cell line for basal-like breast carcinoma MDA-MB-231, then traced secondary and tertiary effects of this knockdown to LAMA4, a laminin encoding gene that contributes to the phenotype of triple-negative breast cancer. LAMA4-regulating miRNA miR-4274 and its host gene SORCS2 were highlighted as intermediate regulators of the expression levels of LAMA4, which correlated in a basal-like breast carcinoma sample subset of TCGA to the levels of SORCS2 negatively. Overall, our study points that the secondary and tertiary layers of regulatory interactions are certainly underappreciated. As these types of molecular event may significantly contribute to the formation of the cell phenotypes after RNA interference based knockdowns, further studies of multilayered molecular networks affected by RNAi are warranted.
U2 - 10.3389/fmolb.2019.00122
DO - 10.3389/fmolb.2019.00122
M3 - SCORING: Journal article
C2 - 31781574
VL - 6
SP - 122
JO - FRONT MOL BIOSCI
JF - FRONT MOL BIOSCI
SN - 2296-889X
ER -
