IFN-α/BST2在宫颈癌发生发展中的作用与机制

doi:10.12280/gjszjk.20250547

摘要/Abstract

摘要：

宫颈癌是全球女性最常见的恶性肿瘤之一，其发生发展与高危型人乳头瘤病毒（human papilloma virus，HPV）的持续感染密切相关。α干扰素（interferon-α，IFN-α）作为一种重要的免疫调节细胞因子，被用于宫颈癌的辅助治疗，但其疗效存在个体差异，机制未明。骨髓基质细胞抗原2（bone marrow stromal cell antigen 2，BST2）是IFN-α下游的关键效应分子，具有独特的抗病毒功能。IFN-α通过诱导包括BST2在内的干扰素刺激基因发挥抗病毒与抗肿瘤作用。研究发现，BST2在宫颈癌组织中异常高表达，具有双重功能：一方面作为天然免疫因子限制病毒释放；另一方面在肿瘤微环境中通过激活核因子κB（nuclear factor-κB，NF-κB）、丝裂原激活的蛋白激酶（mitogen-activated protein kinase，MAPK）/胞外信号调节激酶（extracellular signal-regulated kinase，ERK）等信号通路促进肿瘤细胞增殖、抑制凋亡，并调控巨噬细胞向M2型极化及抑制自然杀伤细胞毒性，从而塑造免疫抑制性微环境，促进免疫逃逸。此外，BST2表达受DNA低甲基化及长链非编码RNA FGD5反义链1（long non-coding RNA FGD5 antisense 1，lncRNA FGD5-AS1）/微RNA-129-5p（microRNA-129-5p，miR-129-5p）等表观遗传机制调控，IFN-BST2-人类白细胞抗原（human leukocyte antigen，HLA）轴在肿瘤免疫识别与逃逸中发挥作用。综述IFN-α/BST2与宫颈癌发生发展的相互关系及分子机制，为开发新的靶向治疗策略提供依据。

关键词: 干扰素α, 骨髓基质抗原2, 宫颈肿瘤, 癌, 细胞增殖, 细胞凋亡, DNA甲基化

Abstract:

Cervical cancer is one of the most common malignancies in women worldwide, and its initiation and progression are closely associated with the persistent infection of high-risk human papilloma virus (HPV). Interferon-α (IFN-α), as an important immunoregulatory cytokine, has been used as an adjuvant therapy for cervical cancer, but its efficacy varies among individuals and the mechanisms remain unclear. Bone marrow stromal cell antigen 2 (BST2) is a key downstream effector of IFN-α with distinctive antiviral function. IFN-α exerts antiviral and antitumor effects by inducing interferon-stimulated genes including BST2. Two main roles of the overexpressed BST2 in cervical cancer are: on one hand, BST2 as an innate immune factor restricts viral release; on the other hand, BST2 within the tumor microenvironment promotes tumor cell proliferation, inhibits apoptosis, and regulates macrophage polarization toward the M2 phenotype and suppresses natural killer cell cytotoxicity by activating signaling pathways such as nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) /extracellular signal-regulated kinase (ERK) pathway, thereby shaping an immunosuppressive microenvironment and facilitating immune evasion. In addition, BST2 expression is regulated by epigenetic mechanisms such as DNA hypomethylation and the long non-coding RNA FGD5 antisense 1 (lncRNA FGD5-AS1) /microRNA-129-5p (miR-129-5p) axis. The IFN-BST2-HLA (human leukocyte antigen) axis also plays a role in immune recognition and escape. This review summarizes the relationship and molecular mechanisms between IFN-α/BST2 and the occurrence and development of cervical cancer, providing a basis for developing new targeted therapies.

Key words: Interferon-alpha, Bone marrow stromal antigen 2, Uterine cervical neoplasms, Carcinoma, Cell proliferation, Apoptosis, DNA methylation

刘佩芬, 索静. IFN-α/BST2在宫颈癌发生发展中的作用与机制[J]. 国际生殖健康/计划生育杂志, 2026, 45(2): 150-153.

LIU Pei-fen, SUO Jing. The Role and Mechanism of the IFN-α/BST2 in the Occurrence and Development of Cervical Cancer[J]. Journal of International Reproductive Health/Family Planning, 2026, 45(2): 150-153.

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