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CXCL12-regulated miR-370-3p functions as a tumor suppressor gene by targeting HMGA2 in nonfunctional pituitary

Feng Cai1, Congxin Dai2, Shasha Chen3

  • 1The Dept. of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, The City of Hangzhou, Zhejiang Province, PR China.

Molecular and Cellular Endocrinology
|March 12, 2019
PubMed

Insights

The CXCL12/miR-370-3p/HMGA2 pathway impacts pituitary tumor growth. CXCL12 reduces miR-370-3p, increasing HMGA2 and promoting nonfunctional pituitary adenoma (NFPA) invasiveness.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Noncoding gene silencing at the DLK1-MEG3 locus is specific to human nonfunctional pituitary adenomas (NFPAs).
  • The precise molecular mechanisms driving this silencing and its role in NFPA pathogenesis remain largely unknown.

Purpose of the Study:

  • To investigate the effect of CXCL12 on microRNA (miRNA) expression within the DLK1-MEG3 locus in NFPAs.
  • To elucidate the impact of these molecular changes on NFPA phenotypic alterations and clinical features.

Main Methods:

  • Screening of differentially expressed miRNAs in human NFPA samples treated with CXCL12.
  • In vitro prediction and verification of miRNA target mRNAs.
  • Assessment of tumor phenotypic alterations and correlation with clinical features in 51 NFPA samples.

Main Results:

  • CXCL12 treatment led to decreased expression of miR-370 in NFPAs.
  • miR-370-3p was identified and validated as a tumor suppressor targeting HMGA2.
  • HMGA2 overexpression was found to counteract the antitumor function of miR-370-3p.
  • Downregulation of miR-370-3p and significant upregulation of HMGA2 were observed in high-grade NFPAs.

Conclusions:

  • The CXCL12/miR-370-3p/HMGA2 signaling pathway plays a critical role in the growth and invasiveness of NFPAs.
  • This pathway represents a potential therapeutic target for managing NFPA progression.
Keywords:
CXCL12HMGA2Nonfunctional pituitary adenomasTumor invasionTumor proliferationmiR-370–3p

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