Unknown

Dataset Information

0

MicroRNA-211 Loss Promotes Metabolic Vulnerability and BRAF Inhibitor Sensitivity in Melanoma.


ABSTRACT: The clinical management of malignant melanoma remains a challenge because these tumors are intrinsically aggressive and prone to therapeutic resistance. MicroRNA (miR)-211 is an emerging melanoma oncogene. Melanoma metabolism adapts to promote survival, including in response to BRAFV600E inhibition, but how miR-211 participates in this process is unknown. Here, we generated miR-211 loss-of-function cell lines using CRISPR/Cas9 technology and show that miR-211 loss slowed growth and invasion in vitro, inhibited phosphoinositol-3-kinase signaling, and inhibited melanoma growth in vivo. miR-211 deficiency rendered melanoma cells metabolically vulnerable by attenuating mitochondrial respiration and tricarboxylic acid cycling. miR-211 was up-regulated by the BRAF inhibitor vemurafenib and in vemurafenib-resistant melanoma cells, with miR-211 loss rendering them more drug sensitive. miR-211 loss represents a "two-pronged" anticancer strategy by inhibiting both critical growth-promoting cell signaling pathways and rendering cells metabolically vulnerable, making it an extremely attractive and specific candidate combinatorial therapeutic target in melanoma.

SUBMITTER: Sahoo A 

PROVIDER: S-EPMC6309654 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

MicroRNA-211 Loss Promotes Metabolic Vulnerability and BRAF Inhibitor Sensitivity in Melanoma.

Sahoo Anupama A   Sahoo Sanjaya K SK   Joshi Piyush P   Lee Bongyong B   Perera Ranjan J RJ  

The Journal of investigative dermatology 20180801 1


The clinical management of malignant melanoma remains a challenge because these tumors are intrinsically aggressive and prone to therapeutic resistance. MicroRNA (miR)-211 is an emerging melanoma oncogene. Melanoma metabolism adapts to promote survival, including in response to BRAF<sup>V600E</sup> inhibition, but how miR-211 participates in this process is unknown. Here, we generated miR-211 loss-of-function cell lines using CRISPR/Cas9 technology and show that miR-211 loss slowed growth and in  ...[more]

Similar Datasets

2019-01-02 | GSE109378 | GEO
| PRJNA430713 | ENA
| S-EPMC4951241 | biostudies-literature
| S-EPMC5815895 | biostudies-literature
| S-EPMC8619236 | biostudies-literature
| S-EPMC9768695 | biostudies-literature
| S-EPMC7669662 | biostudies-literature
| S-EPMC5654168 | biostudies-literature
2018-01-18 | GSE107576 | GEO
| S-EPMC7024013 | biostudies-literature