MicroRNA-221 promotes tumor progression by targeting HHIP in human glioblastoma

Liang Chang1, Lisheng Yin1, Dongzhi Zhang1

  • 1Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, China.

Abstract

Insights

MicroRNA-221 (miR-221) is upregulated in glioblastoma (GBM), promoting tumor growth and spread. Inhibiting miR-221 and its target, HHIP, suppressed GBM progression, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are implicated in various cancers, with aberrant expression observed in glioblastoma (GBM).
  • MicroRNA-221 (miR-221) is recognized as an oncogene in several cancers, but its specific role in GBM remains largely unelucidated.
  • This study investigates the expression and functional significance of miR-221 in GBM.

Purpose of the Study:

  • To determine the expression level of miR-221 in glioblastoma.
  • To evaluate the functional role of miR-221 in GBM cell proliferation, migration, and invasion.
  • To elucidate the underlying molecular mechanisms, including identifying miR-221 targets in GBM.

Main Methods:

  • Quantitative real-time PCR (qPCR) and Western blotting were employed to assess miR-221 and human hedgehog-interacting protein (HHIP) expression.
  • Cellular assays including MTT, colony formation, wound healing, and Transwell invasion assays were performed on miR-221-inhibited GBM models.
  • In vivo studies utilized a subcutaneous xenograft model to evaluate tumor growth. Bioinformatics, dual-luciferase reporter assays, and Western blotting confirmed the interaction between miR-221 and HHIP.

Main Results:

  • Real-time PCR confirmed elevated miR-221 expression in GBM tissues and cell lines (A172, U251, T98G).
  • Downregulation of miR-221 significantly inhibited GBM cell proliferation, migration, and invasion in vitro, and suppressed tumor growth in vivo.
  • Human hedgehog-interacting protein (HHIP) was identified and validated as a direct target of miR-221. Silencing HHIP expression abrogated the inhibitory effects of miR-221 knockdown on GBM progression.

Conclusions:

  • MicroRNA-221 is upregulated in glioblastoma and acts as an oncogene by promoting tumor progression.
  • The oncogenic function of miR-221 in GBM is mediated through the suppression of its target, HHIP.
  • Targeting the miR-221/HHIP axis presents a promising therapeutic strategy for glioblastoma treatment.

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