Related Experiment Video

Updated: Jul 15, 2025

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.0K

Let-7g Upregulation Attenuated the KRAS-PI3K-Rac1-Akt Axis-Mediated Bioenergetic Functions

Kuang-Chen Hung1,2,3, Ni Tien4, Da-Tian Bau5

  • 1Division of Neurosurgery, Department of Surgery, Taichung Army Force General Hospital, Taichung 41152, Taiwan.

Cells
|September 28, 2023
PubMed

Insights

Naringenin (NGN) targets KRAS-p110α interaction in nasopharyngeal carcinoma (NPC) cells, inhibiting glycolysis and mitochondrial OXPHOS via let-7g upregulation and MCPIP1 suppression, ultimately inducing apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Aberrant signaling pathway activation drives cancer metabolic reprogramming.
  • Targeting signaling modulators offers a promising cancer therapeutic strategy.

Purpose of the Study:

  • To investigate the effect of naringenin (NGN) on signaling pathways and metabolic dysfunction in nasopharyngeal carcinoma (NPC) cells.
  • To elucidate the role of KRAS, let-7g, and MCPIP1 in NGN-induced apoptosis.

Main Methods:

  • Subcellular fractionation, coimmunoprecipitation, and biochemical analyses were employed.
  • Gene manipulation using let-7g mimic and inhibitor.
  • Experiments focused on lipid rafts and MCPIP1 ribonuclease activity.

Main Results:

  • NGN decreased KRAS-p110α interaction in lipid rafts, disrupting PI3K-Rac1-Akt signaling.
  • This disruption led to metabolic dysfunction in glycolysis and mitochondrial OXPHOS, inducing apoptosis in NPC cells.
  • NGN upregulated let-7g by inhibiting MCPIP1-mediated degradation, suppressing oncogenic KRAS signaling.

Conclusions:

  • NGN effectively inhibits NPC cell proliferation by targeting the KRAS-PI3K-Akt axis and metabolic pathways.
  • The NGN-MCPIP1-let-7g interaction is crucial for modulating cellular metabolism and inducing apoptosis in NPC.
  • NGN represents a potential therapeutic agent for nasopharyngeal carcinoma by re-establishing metabolic homeostasis.
Keywords:
KRASMCPIP1bioenergetic metabolismlet-7gnaringenin

More Related Videos

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells09:20

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells

Published on: July 6, 2021

2.4K
The Soft Agar Colony Formation Assay08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

111.9K

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...
3.6K
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...
3.8K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.6K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.3K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
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...
6.3K