Long non-coding RNA MALAT1 promotes angiogenesis and immunosuppressive properties of HCC cells by sponging miR-140.
Am J Physiol Cell Physiol
; 318(3): C649-C663, 2020 03 01.
Article
en En
| MEDLINE
| ID: mdl-31693399
ABSTRACT
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer in adults. Previous studies in our laboratory found that long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was upregulated in HCC cells, which could affect the metastasis and invasion of HCC. However, the underlying mechanism remains unknown. Herein, we studied the interaction between MALAT1 and miR-140 on the regulation of angiogenesis and immunosuppressive properties. We revealed that the expression of MALAT1 and VEGF-A was significantly increased in HCC cells. Knockdown of MALAT1 in HCC cells suppressed the production of VEGF-A, impaired the angiogenesis of HUVECs, and facilitated the polarization of macrophage toward the M1 subset. Mechanistically, the interaction between MALAT1 and miR-140 or between miR-140 and VEGF-A was confirmed by multiple assays. Besides, a negative correlation between MALAT1 and miR-140 was found in HCC tissues. Furthermore, miR-140 inhibition significantly increased VEGF-A expression, promoted angiogenesis of HUVECs, and redirected the polarization of macrophages toward the M2 subset. In addition, in vivo studies also verified the regulatory network of the MALAT1/miR-140 axis on VEGF-A in HCC progression. In summary, this study revealed the mechanism that MALAT1 worked as a putative HCC promotor via inhibiting miR-140. Therefore, targeting MALAT1 or miR-140 might alleviate the progression of HCC in the future.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma Hepatocelular
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MicroARNs
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ARN Largo no Codificante
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Tolerancia Inmunológica
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Neoplasias Hepáticas
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Neovascularización Patológica
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Am J Physiol Cell Physiol
Asunto de la revista:
FISIOLOGIA
Año:
2020
Tipo del documento:
Article