Long non-coding RNA LSINCT5 inactivates Wnt/β-catenin pathway to regulate MCF-7 cell proliferation and motility through targeting the miR-30a

长链非编码 RNA LSINCT5 通过靶向 miR-30a 抑制 Wnt/β-catenin 通路来调控 MCF-7 细胞增殖和运动

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作者:Guizhi Zhang, Wenbo Song

Background

Breast cancer (BC) is the most common malignant tumor among women. Earlier studies showed that long stress-induced non-coding transcript 5 (LSINCT5) was implicated in BC. However, the potential mechanisms of LSINCT5 in BC is still elusive.

Conclusions

The present results uncovered that LSINCT5 knockdown suppressed BC growth and metastasis via the miR-30a/Wnt/β-catenin axis, and it served as a potential therapeutic target for early diagnosis and treatment of BC patients..

Methods

Relative expression of LSINCT5 in BC tissues and cells were quantified by quantitative real-time reverse transcription PCR (qRT-PCR). shRNA was employed to specifically knockdown endogenous LSINCT5 in BC cells. Cell growth and invasion activity of BC cells was assessed by colony formation and transwell migration assay, respectively. The association between LSINCT5 and miR-30a was conducted by luciferase reporter assay. Subcutaneous injection of sh-LSINCT5 transfected MCF-7 cells into the ventral regions of mice to form tumors. Mice were divided into three groups (n=10): control group, sh-NC group, sh-LSINCT5 group (sh-NC or sh-LSINCT5 transfected MCF-7 cells injected into mice). Tumor weight was checked after 30 days post-injection.

Results

LSINCT5 was significantly up-regulated in BC tissues and cells. LSINCT5 knockdown suppressed proliferation, invasion, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. LSINCT5 acted as a sponge molecule and targeted miR-30a in BC cells. Further mechanistic study exhibited that overexpression of LSINCT5 promoted the expression of Wnt/β-catenin-related proteins (β-catenin, TCF4, and c-Myc). In vivo, xenograft nude mice experiment indicated sh-LSINCT5 inhibited tumor growth and motility by targeting miR-30a through modulating Wnt/β-catenin pathway. Conclusions: The present results uncovered that LSINCT5 knockdown suppressed BC growth and metastasis via the miR-30a/Wnt/β-catenin axis, and it served as a potential therapeutic target for early diagnosis and treatment of BC patients..

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