TPX2 regulated by miR-29c-3p induces cell proliferation in osteosarcoma via the AKT signaling pathway

Dongsheng Zhu1, Xiangfei Xu1, Ming Zhang1

  • 1Department of Pediatric Surgery, The First People's Hospital of Lianyungang Affiliated to Xuzhou Medical University, Lianyungang, Jiangsu 222000, P.R. China.

Oncology Letters
|March 28, 2022
PubMed

Insights

Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is upregulated in osteosarcoma, correlating with poor prognosis. MicroRNA-29c-3p inhibits osteosarcoma cell proliferation by downregulating TPX2, suggesting potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma is a primary bone malignancy with limited treatment options.
  • Understanding the molecular mechanisms driving osteosarcoma progression is crucial for developing novel therapies.
  • Targeting protein for Xenopus kinesin-like protein 2 (TPX2) has emerged as a potential factor in cancer development.

Purpose of the Study:

  • To investigate the role of TPX2 in osteosarcoma.
  • To explore the relationship between TPX2 and microRNA-29c-3p (miR-29c-3p) in osteosarcoma.
  • To evaluate TPX2 and miR-29c-3p as potential prognostic biomarkers for osteosarcoma.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) database for TPX2 expression and survival data.
  • Quantitative PCR to assess TPX2 expression in osteosarcoma tissues.
  • Luciferase reporter assays and TargetScan to confirm the interaction between TPX2 and miR-29c-3p.
  • Kaplan-Meier survival analysis to correlate TPX2 levels with patient prognosis.
  • In vitro experiments using small interfering RNA (siRNA) against TPX2 in osteosarcoma cell lines to assess proliferation (MTT assay) and AKT pathway activation (Western blot).

Main Results:

  • TPX2 expression was significantly upregulated in osteosarcoma tissues compared to normal tissues.
  • High TPX2 expression was associated with poorer patient survival.
  • miR-29c-3p was found to directly target and downregulate TPX2 expression.
  • Knockdown of TPX2 using siRNA inhibited osteosarcoma cell proliferation and affected the AKT signaling pathway.
  • miR-29c-3p expression was downregulated in osteosarcoma.

Conclusions:

  • TPX2 is overexpressed in osteosarcoma and linked to unfavorable prognosis.
  • miR-29c-3p acts as a tumor suppressor by targeting and inhibiting TPX2 in osteosarcoma.
  • The miR-29c-3p/TPX2 axis influences osteosarcoma cell proliferation via the AKT pathway.
  • Both TPX2 and miR-29c-3p show potential as prognostic indicators for osteosarcoma.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.7K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.8K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.4K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.0K