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Updated: Jun 27, 2025

Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
CD271 mRNA/hnRNPA2B1 complex promotes proliferation and stemness in oral and head and neck squamous cell carcinoma
Mai Mochizuki1, Rie Shibuya-Takahashi1, Shin-Ichiro Kanno2
1Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori, Japan.
Abstract:
RNAs, such as noncoding RNA, microRNA, and recently mRNA, have been recognized as signal transduction molecules. CD271, also known as nerve growth factor receptor, has a critical role in cancer, although the precise mechanism is still unclear. Here, we show that CD271 mRNA, but not CD271 protein, facilitates spheroid cell proliferation. We established CD271-/- cells lacking both mRNA and protein of CD271, as well as CD271 protein knockout cells lacking only CD271 protein, from hypopharyngeal and oral squamous cell carcinoma lines. Sphere formation was reduced in CD271-/- cells but not in CD271 protein knockout cells. Mutated CD271 mRNA, which is not translated to a protein, promoted sphere formation. CD271 mRNA bound to hnRNPA2B1 protein at the 3'-UTR region, and the inhibition of this interaction reduced sphere formation. In surgical specimens, the CD271 mRNA/protein expression ratio was higher in the cancerous area than in the noncancerous area. These data suggest CD271 mRNA has dual functions, encompassing protein-coding and noncoding roles, with its noncoding RNA function being predominant in oral and head and neck squamous cell carcinoma.
Insights
CD271 messenger RNA (mRNA), not its protein, drives cancer cell proliferation by interacting with hnRNPA2B1. This noncoding RNA function is key in head and neck squamous cell carcinoma.
Area of Science:
- Molecular biology
- Cancer research
- RNA biology
Background:
- RNAs, including mRNA, act as signaling molecules.
- CD271 (nerve growth factor receptor) is implicated in cancer, but its mechanism is unclear.
Purpose of the Study:
- To investigate the role of CD271 mRNA versus protein in cancer proliferation.
- To elucidate the mechanism of CD271's function in oral and head and neck squamous cell carcinoma.
Main Methods:
- Generated CD271 knockout and CD271 mRNA/protein knockout cell lines.
- Assessed spheroid cell proliferation and sphere formation.
- Analyzed CD271 mRNA and hnRNPA2B1 protein interaction.
- Examined CD271 mRNA/protein ratios in surgical specimens.
Main Results:
- CD271 mRNA, not protein, significantly enhanced spheroid cell proliferation.
- Sphere formation decreased in CD271-/- cells but not in protein knockout cells.
- Mutated CD271 mRNA lacking protein translation still promoted proliferation.
- CD271 mRNA binds hnRNPA2B1 at the 3'-UTR, and inhibiting this interaction reduced proliferation.
- Higher CD271 mRNA/protein ratios were observed in cancerous tissues.
Conclusions:
- CD271 mRNA possesses dual coding and noncoding functions.
- The noncoding RNA function of CD271 mRNA is predominant in oral and head and neck squamous cell carcinoma.
- CD271 mRNA's interaction with hnRNPA2B1 is crucial for cancer cell proliferation.
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10:26RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma
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