HOXA10-AS Enhances Gastric Cancer Cell Proliferation, Migration, and Invasion via the p38 MAPK/STAT3 Signaling Pathway

  • 0Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, China.

|

|

Summary

This summary is machine-generated.

Long noncoding RNA HOXA10-AS promotes gastric cancer (GC) progression by upregulating HOXA10 expression, which activates the p38 MAPK/STAT3 pathway. This study reveals HOXA10-AS as a potential therapeutic target for gastric cancer.

Area Of Science

  • Oncology
  • Molecular Biology
  • Genetics

Background

  • Gastric cancer (GC) is a significant global health issue, with over 1 million new cases annually.
  • Long noncoding RNAs (lncRNAs) are increasingly recognized for their role in GC progression.

Purpose Of The Study

  • To investigate the role and mechanism of lncRNA HOXA10 antisense RNA (HOXA10-AS) in modulating the malignant properties of GC cells.
  • To elucidate the regulatory pathway involving HOXA10-AS, HOXA10, and miR-29a/b/c-3p in GC.

Main Methods

  • Quantitative reverse transcription PCR (RT-qPCR) for gene expression analysis.
  • Cellular assays (colony formation, Transwell) to assess cell proliferation, invasion, and migration.
  • Molecular techniques including RNA immunoprecipitation, RNA pulldown, and luciferase assays to determine gene interactions.
  • Western blot analysis for epithelial-mesenchymal transition (EMT) markers.

Main Results

  • HOXA10-AS was highly expressed in GC cells and its silencing reduced proliferation, invasion, migration, and EMT.
  • HOXA10-AS positively regulated HOXA10 expression via interaction with miR-29a/b/c-3p.
  • Overexpression of HOXA10 reversed the inhibitory effects of HOXA10-AS knockdown.
  • HOXA10-AS activated the p38 MAPK/STAT3 signaling pathway by upregulating HOXA10.

Conclusions

  • HOXA10-AS promotes GC cell growth, migration, invasion, and EMT by upregulating HOXA10 expression.
  • The HOXA10-AS/miR-29a/b/c-3p/HOXA10 axis activates the p38 MAPK/STAT3 signaling pathway, driving GC progression.
  • HOXA10-AS represents a potential therapeutic target for gastric cancer treatment.

Related Concept Videos

mTOR Signaling and Cancer Progression 03:03

3.7K

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...

Hedgehog Signaling Pathway 02:33

7.3K

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...

Interactions Between Signaling Pathways 01:19

6.2K

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...

Role Of Notch Signalling In Intestinal Stem Cell Renewal 01:12

2.0K

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

Small GTPases - Ras and Rho 01:24

3.9K

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:

Guanine nucleotide exchange factors or GEF,
GTPase-activating proteins or GAPs, and
Guanine nucleotide-dissociation inhibitors or GDIs.

The GEF activates the GTPase by exchanging the bound-GDP with GTP. The...

Regulation of Angiogenesis and Blood Supply 01:24

2.5K

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...