LncRNA MALAT1 Promotes Cancer Metastasis in Osteosarcoma via Activation of the PI3K-Akt Signaling Pathway

Cell Physiol Biochem. 2018;51(3):1313-1326. doi: 10.1159/000495550. Epub 2018 Nov 27.


Background/aims: LncRNAs have been reported to be vital regulators of the progression of osteosarcoma, although the underlying mechanisms are not completely understood.

Methods: The levels of MALAT1 and miR-129-5p expression were measured using qRT-PCR. Cell growth was determined using the CCK-8 and colony formation assays. Cell migration and invasion were detected using the wound healing and Transwell invasion assays, respectively. Tumor growth was determined with a xenograft model.

Results: MALAT1 was significantly up-regulated in osteosarcoma tissues compared with adjacent non-tumor soft tissues. Overexpression of MALAT1 promoted osteosarcoma cell proliferation, migration, and invasion in vitro and enhanced tumor growth in a tumor xenograft mouse model. MALAT1 promoted osteosarcoma progression by modulating stem cell-like properties. Moreover, rescue experiment and luciferase reporter assay results indicated that MALAT1 modulates RET expression by sponging miR-129-5p in osteosarcomas. Furthermore, MALAT1 augmented the expression of downstream proteins of the RET-Akt pathway. MALAT1 was consistently significantly increased in osteosarcoma tissues and MALAT1 expression was positively correlated with tumor size and metastasis. High expression of MALAT1 was significantly associated with poor outcomes in patients with osteosarcomas. MALAT1 expression was positively related to RET and negatively related to miR-129-5p in osteosarcoma samples and xenograft tumors. MALAT1 functioned as an oncogenic lncRNA in osteosarcomas and was as an independent prognostic indicator.

Conclusion: Our data revealed for the first time that MALAT1 increases stem cell-like properties by up-regulating RET via sponging miR-129-5p, and thus activates the PI3K-Akt signaling pathway and provides potential therapeutic targets for osteosarcoma treatment.

Keywords: Long non-coding RNA (lncRNA); Metastasis; Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1); Osteosarcoma; Prognosis; Proliferation; Stemness.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-ret / genetics
  • RNA, Long Noncoding / genetics*
  • Signal Transduction


  • MALAT1 long non-coding RNA, human
  • Malat1 long non-coding RNA, mouse
  • MicroRNAs
  • Mirn129 microRNA, human
  • RNA, Long Noncoding
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Proto-Oncogene Proteins c-akt