miR-372 regulates glioma cell proliferation and invasion by directly targeting PHLPP2

Xin Chen1, Bin Hao, Guosheng Han

  • 1Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.

Insights

MicroRNA-372 (miR-372) acts as an oncogene in glioma by promoting cancer cell growth and spread. Inhibiting miR-372 suppresses tumor development by targeting PHLPP2 and affecting the PI3K/Akt pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are implicated in cancer development and progression.
  • The specific role of microRNA-372 (miR-372) in glioma pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the function and mechanism of miR-372 in glioma.
  • To determine if miR-372 acts as an oncogene or tumor suppressor in glioma.

Main Methods:

  • Quantitative real-time PCR to measure miR-372 expression in glioma tissues and cell lines.
  • Cell proliferation, invasion, apoptosis, and cell cycle assays after miR-372 knockdown.
  • Xenograft mouse models to assess tumor growth inhibition.
  • Luciferase reporter assays to confirm direct targeting of PHLPP2 by miR-372.
  • Western blotting to analyze protein expression, including PI3K/Akt pathway components.

Main Results:

  • miR-372 was significantly upregulated in glioma cell lines and tissues.
  • Downregulation of miR-372 inhibited glioma cell proliferation and invasion, induced apoptosis, and caused G1/S cell cycle arrest.
  • miR-372 directly targets the 3'-untranslated region of PHLPP2, and its expression is inversely correlated with PHLPP2 levels in glioma.
  • Knockdown of PHLPP2 reversed the inhibitory effects of miR-372 inhibition.
  • miR-372 knockdown suppressed the phosphorylation of Akt, mTOR, and P70S6K in the PI3K/Akt pathway.

Conclusions:

  • miR-372 functions as an oncogenic miRNA in glioma by targeting PHLPP2.
  • miR-372 promotes glioma progression through the PI3K/Akt signaling pathway.

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...
5.1K
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...
3.6K
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...
4.0K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
4.6K
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...
6.3K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
32.1K