CD271 mRNA/hnRNPA2B1 complex promotes proliferation and stemness in oral and head and neck squamous cell carcinoma

Sep 21, 2026

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RNAs—including noncoding RNA, microRNA, and mRNA—act as signal transduction molecules. CD271 (nerve growth factor receptor) is implicated in cancer, yet its mechanism remains unclear. The study shows CD271 mRNA, but not CD271 protein, enhances spheroid proliferation in oral and hypopharyngeal squamous cell carcinoma models. CD271 mRNA (not translated to protein) promotes sphere formation, binds hnRNPA2B1 at the 3′-UTR, and its interaction inhibition reduces sphere growth. Patient specimens show higher CD271 mRNA/protein ratios in cancerous regions, supporting a predominant noncoding function in this disease context.

LanguageEnglish

CategoryHealthcare

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Pages14

Reading Time35 min

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Abstract

Introduction

Materials and Methods

Received: 17 October 2023 Revised: 1 April 2024 Accepted: 4 April 2024 DOI: 10. 1111/cas.16187 OR I G I NAL ART I C L E 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 | Shungo Adachi3,4 | Haruna Fujimori1 | Akira Nakazato1 | Keitaro Fujii1 | Shinkichi Morita1,5 | Satoshi Saijoh1 | Tomoko Yamazaki1 | Takayuki Imai1,5 | Yukinori Asada1,5 | Kazunori Yamaguchi6 | Jun Yasuda6 | Norihisa Shindo7 | Kazuo Sugamura6 | Keiichi Tamai1 1Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori, Japan 2IDAC Fellow Research Group for DNA Repair and Dynamic Proteome Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan 3 Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan 4Department of Proteomics, National Cancer Center Research Institute, Tokyo, Japan 5Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, Japan 6Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, Japan 7Cancer Chromosome Biology Unit, Miyagi Cancer Center Research Institute, Natori, Japan Correspondence Mai Mochizuki, Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1 Nodayama, MedeshimaShiote, Natori, Miyagi 981-1293, Japan. Email: mcc2f. mochi+[paper@gmail.com](paper@gmail.com) Funding information Japan Society for the Promotion of Science, Grant/Award Number: 19K08430, 20K09701, 21H02396, 21K07137, 21K07186, 21K07973, 22H02225, 22K07974, 22K08085, 22K09678 and 22K09696; Japan Agency for Medical Research and Development, Grant/Award Number: 22nk0101583h0001; Kobayashi Foundation for Cancer Research; Takeda Medical Research Foundation; Core Research for Evolutional Science and Technology, Grant/Award Number: JPMJCR20E6 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 toa protein, promoted sphere formation. CD271 mRNA bound to hnRNPA2B1 protein atthe 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. K E Y WO R D S CD271, head and neck squamous cell carcinoma, hnRNPA2B1, mRNA, oral squamous cell carcinoma This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. 1 | INTRODUCTION Sustained proliferative signaling is an essential hallmark of cancer.1 Proliferative signals are transmitted by several membrane receptors, including epidermal growth factor receptor and fibroblast growth factor receptor. CD271, also known as neural growth factor receptor, has a critical role in neuronal development.2 Although CD271 la

FAQs

What does the study show about CD271 mRNA versus CD271 protein in cancer cells?

CD271 mRNA facilitates spheroid cell proliferation, while CD271 protein does not show the same effect. CD271−/− cells lacking both CD271 mRNA and protein show reduced sphere formation, whereas CD271 protein knockout cells lacking only the protein do not show the reduction.

How does CD271 mRNA promote proliferation and stemness?

Mutated CD271 mRNA that is not translated to a protein still promotes sphere formation. CD271 mRNA binds hnRNPA2B1 at the 3′-UTR region, and inhibiting this interaction reduces sphere formation.

What evidence links CD271 RNA/protein expression to human oral and head and neck squamous cell carcinoma?

In surgical specimens, the CD271 mRNA/protein expression ratio is higher in cancerous tissue than in noncancerous tissue. These findings support dual functions of CD271, with a predominant noncoding RNA role in this cancer type.

Sep 21, 2026

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