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Upregulation of SNHG12 accelerates cell proliferation, migration, invasion and restrain cell apoptosis in breast cancer by enhancing regulating SALL4 expression via sponging miR-15a-5p

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Jian-Hua Yuan, Wei-Xue Li, Chen Hu,  Bo Zhang

Abstract:

Breast cancer (BC) is malignant cancer that threatens the health of millions of females worldwide. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) has been identified as an oncogene in multiple cancers. However, the regulatory role of SNHG12 in BC cell progression is still obscured. The levels of SNHG12, miR-15a-5p, and Sal-like 4 (SALL4) in BC tumor tissues and cells were measured by qRT-PCR. Cell viability, apoptosis, migration, and invasion were examined by CCK8, flow cytometry, and transwell assay, respectively. The interaction between miR-15a-5p and SNHG12 or SALL4 was evaluated by dual-luciferase reporter assay. Protein expression of SALL4 was analyzed by western blot. Xenograft mice were established by subcutaneously injecting BC cells stably transfected with sh-SNHG12 and sh-NC. SNHG12 and SALL4 expressions were upregulated whereas miR-15a-5p was downregulated in BC tumors compared with normal tissues. Besides, miR-15a-5p was correlated with SNHG12 and SALL4 inversely as calculated by Pearson’s correlation coefficient. More importantly, SNHG12 knockdown attenuated BC tumor growth in vitro and in vivo. Subsequently, dual-luciferase reporter assay confirmed the interaction between miR-15a-5p and SNHG12 or SALL4. The rescue experiments revealed that miR-15a-5p inhibitor restored SNHG12 silencing induced inhibition on BC cell proliferation, migration, invasion, and promotion of apoptosis. Additionally, SNHG12 was found to accelerate BC cell progression by absorbing miR-15a-5p to enhance SALL4 expression. SNHG12 promotes cell proliferation, migration, and invasion but suppresses apoptosis in BC by upregulating SALL4 expression via sponging miR-15a-5p, representing potential targets for the development of novel diagnosis and treatment methods.

Received date: 08/08/2019

Accepted date: 11/13/2019

Ahead of print publish date: 05/06/2020

Issue: 4/2020

Volume: 67

Pages: 861 — 870

Keywords: SNHG12, miR-15a-5p, SALL4, progression, breast cancer

DOI: 10.4149/neo_2020_190808N731

Pubmed

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