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Long noncoding RNA CASC11 promotes osteosarcoma metastasis by suppressing degradation of snail mRNA

Kaifang Song1, Xiang Yuan2,3, Guifang Li1

  • 1Department of Pulmonary Tumor Surgery, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology Luoyang 471003, Henan Province, China.

American Journal of Cancer Research
|March 26, 2019
PubMed

Insights

Cancer susceptibility candidate 11 (CASC11) promotes osteosarcoma (OS) metastasis by stabilizing Snail mRNA. Targeting CASC11 may offer a new therapeutic strategy for OS patients with poor prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osteosarcoma (OS) is a prevalent bone cancer in adolescents.
  • Long noncoding RNAs (lncRNAs) are implicated in cancer progression, with CASC11 identified as an oncogene in various cancers.
  • The role of CASC11 in OS metastasis is not fully understood.

Purpose of the Study:

  • To investigate the role and mechanism of CASC11 in osteosarcoma metastasis.
  • To explore CASC11 as a potential prognostic biomarker and therapeutic target for OS.

Main Methods:

  • Quantitative analysis of CASC11 expression in OS tissues and correlation with clinical data.
  • In vitro and in vivo gain- and loss-of-function assays to assess CASC11's impact on OS cell behavior.
  • Investigation of CASC11's interaction with Snail mRNA and microRNAs (miRNAs).
  • Evaluation of CASC11-specific siRNAs in inhibiting tumor metastasis.

Main Results:

  • CASC11 expression is significantly elevated in OS tissues compared to noncancerous tissues.
  • High CASC11 expression correlates with advanced clinical stage, distant metastasis, and poor prognosis in OS patients.
  • CASC11 promotes OS cell migration, invasion, epithelial-mesenchymal transition (EMT), and metastasis both in vitro and in vivo.
  • CASC11 enhances Snail mRNA stability, thereby inhibiting the repressive effects of specific miRNAs (miR-122, miR-145, miR-211, miR-34a, miR-137) on Snail.
  • CASC11-specific siRNAs effectively inhibit tumor metastasis in vivo.

Conclusions:

  • CASC11 plays a crucial role in promoting osteosarcoma metastasis through Snail mRNA stabilization.
  • CASC11 represents a potential prognostic biomarker for OS.
  • CASC11 emerges as a promising novel therapeutic target for osteosarcoma.
Keywords:
lncRNAmetastasismicroRNAstability

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