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SphK1-targeted miR-6784 inhibits functions of skin squamous cell carcinoma cells.


ABSTRACT: Sphingosine kinase 1 (SphK1) is overexpressed in skin squamous cell carcinoma (SCC). It has emerged as a novel therapeutic oncotarget. The current study identified a novel SphK1-targeting microRNA, microRNA-6784 (miR-6784). Here, we show that miR-6784 is located at the cytoplasm of A431 skin SCC cells. It directly binds to SphK1 mRNA. Ectopic overexpression of miR-6784 inhibited SphK1 3'-untranslated region (UTR) luciferase activity and downregulated its expression. Moreover, miR-6784 overexpression caused ceramide accumulation in skin SCC cells. Functional studies in established (A431 and SCC9) and primary skin SCC cells revealed that miR-6784 overexpression inhibited cell viability, proliferation, migration, and invasion. It also simultaneously provoked apoptosis activation. Conversely, miR-6784 silencing by antagomiR-6784 induced SphK1 elevation and augmented A431 cell proliferation, migration, and invasion. miR-6784 overexpression-induced anti-A431 cell activity was inhibited by the expression of an UTR-null SphK1 construct. CRISPR/Cas9-induced SphK1 knockout inhibited A431 cell growth. Importantly, miR-6784 was completely ineffective when treating SphK1-knockout A431 cells. Collectively, miR-6784 silences SphK1 and inhibits skin SCC cell progression.

SUBMITTER: Gong ZH 

PROVIDER: S-EPMC7906188 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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SphK1-targeted miR-6784 inhibits functions of skin squamous cell carcinoma cells.

Gong Zhen-Hua ZH   Ji Jiang J   Yao Jian J   Ji Jian-Feng JF   Jiang Yasu Y   Gao Gang G   Feng Zhou Z  

Aging 20210119 3


Sphingosine kinase 1 (SphK1) is overexpressed in skin squamous cell carcinoma (SCC). It has emerged as a novel therapeutic oncotarget. The current study identified a novel SphK1-targeting microRNA, microRNA-6784 (miR-6784). Here, we show that miR-6784 is located at the cytoplasm of A431 skin SCC cells. It directly binds to <i>SphK1</i> mRNA. Ectopic overexpression of miR-6784 inhibited <i>SphK1</i> 3'-untranslated region (UTR) luciferase activity and downregulated its expression. Moreover, miR-6  ...[more]

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