LOC101930370/MiR-1471 Axis Modulates the Hedgehog Signaling Pathway in Breast Cancer

Cell Physiol Biochem. 2018;48(3):1139-1150. doi: 10.1159/000491980. Epub 2018 Jul 24.

Abstract

Background/aims: Non-coding RNAs (ncRNAs) play vital regulatory roles in many tumors. However, the functional roles of these transcripts responsible for their dysregulation in breast cancer (BC) are not thoroughly understood.

Methods: We examined the expression of microRNA miR-1471 in BC specimens. Online analysis tools predicted that lncRNA LOC101930370 might act as an endogenous 'sponge' by competing for miR-1471 binding targets. Luciferase assays were used to prove the interaction of LOC101930370, miR-1471 and SHH. Edu, wound-healing and transwell assays were used to verify the contribution of miR-1471 and LOC101930370 on MCF-7 cells proliferation and metastasis. Gain and loss of function studies were performed to evaluate the relevance of Hedgehog pathway with LOC101930370/miR-1471 regulating axis in MCF-7 cells.

Results: The expression of miR-1471 was markedly downregulated in BC. Inhibition of miR-1471 by LOC101930370 was proved by luciferase assay. Knockdown of LOC101930370 suppressed BC cells progression. MiR-1471 inhibitor resulted in a more aggressive metastasis of MCF-7 cells. Moreover, SHH and Gli-1 expression were significantly suppressed by LOC101930370 knockdown, and upregulated by miR-1471 inhibitor transfection.

Conclusions: Collectively, our study reveals the interaction between LOC101930370 and miR-1471 for the first time. LOC101930370 positively regulates the expression of SHH by sponging miR-1471, which sheds new light on lncRNA-directed diagnostics and therapeutics in BC.

Keywords: Breast cancer; Gli-1; Hedgehog pathway; LOC101930370; MiR-1471; SHH.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Hedgehog Proteins / genetics*
  • Hedgehog Proteins / metabolism
  • Humans
  • MCF-7 Cells
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Signal Transduction*
  • Up-Regulation
  • Young Adult

Substances

  • Hedgehog Proteins