LIN28A/B在肿瘤发生发展中的作用研究进展

doi:10.16288/j.yczz.24-056

遗传 ›› 2024, Vol. 46 ›› Issue (6): 452-465.doi: 10.16288/j.yczz.24-056

LIN28A/B在肿瘤发生发展中的作用研究进展

张译文(), 黄琴(), 吴艳芸, 孙月(), 韦永龙()

云南大学生命科学学院，生命科学研究中心，云南省细胞代谢与疾病重点实验室，昆明 650504

收稿日期:2024-03-07 修回日期:2024-05-07 出版日期:2024-06-20 发布日期:2024-05-23
通讯作者: 韦永龙，博士，研究员，研究方向：肝癌与肝再生。E-mail: weiyl@ynu.edu.cn;孙月，博士，助理研究员，研究方向：肝癌与肝再生。E-mail: yuesun@ynu.edu.cn
作者简介:张译文，硕士研究生，专业方向：细胞生物学。E-mail: yw9273363@163.com
黄琴，博士研究生，专业方向：生物化学与分子生物学。E-mail: 29979752@qq.com
张译文和黄琴并列第一作者。
基金资助:
云南省肿瘤免疫防治研究重点实验室开放课题(KLTIPT-2023-03);云南大学研究生科研创新项目(KC22223021)

Progress on the role of LIN28A/B in tumor development and progression

Zhang Yiwen(), Huang Qin(), Wu Yanyun, Sun Yue(), Wei Yonglong()

Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases School of Life Sciences, Yunnan University, Kunming 650504, China

Received:2024-03-07 Revised:2024-05-07 Published:2024-06-20 Online:2024-05-23
Supported by:
Open project of Yunnan Key Laboratory of Cancer Immunology Prevention and Treatment Research(KLTIPT-2023-03);Graduate Scientific Research Innovation Project of Yunnan University(KC22223021)

摘要/Abstract

摘要：

LIN28A及其同源蛋白LIN28B是高度保守的RNA结合蛋白，在胚胎早期发育、体细胞重编程、葡萄糖代谢以及肿瘤发生发展中具有重要作用。LIN28A/B在乳腺癌等恶性肿瘤中高表达，在肿瘤的起始、维持和转移中均发挥重要作用，并与预后不良相关。研究表明，LIN28A/B主要通过抑制let-7s等microRNA和直接靶向mRNA的方式发挥调控作用。本文主要综述了LIN28A/B在肝癌、乳腺癌、结直肠癌等恶性肿瘤中的功能及其分子调控机制，以期为进一步研究LIN28A/B的作用机制及其在临床治疗中的可能应用提供理论参考。

关键词: LIN28A, LIN28B, let-7 miRNA, 肿瘤发生发展, 治疗靶点

Abstract:

LIN28A and its homolog LIN28B are highly conserved RNA-binding proteins that play important roles in early embryonic development, somatic cell reprogramming, metabolism and tumorigenesis. LIN28A/B are highly expressed in a variety of malignant tumors such as breast cancer. They play important roles in the initiation, maintenance, and metastasis of tumors and are associated with poor prognosis. Previous studies have shown that the main regulatory mechanisms of LIN28A/B include let-7s dependent ways and let-7s independent ways, such as directly targeting mRNA. In this review, we summarize the function and molecular regulatory mechanisms of LIN28A/B in malignant tumors such as liver cancer, breast cancer and colorectal cancer, in order to provide references for further exploring the function and mechanism of LIN28A/B and their possible roles in clinical applications.

Key words: LIN28A, LIN28B, let-7 miRNA, tumor development and progression, therapeutic targets

张译文, 黄琴, 吴艳芸, 孙月, 韦永龙. LIN28A/B在肿瘤发生发展中的作用研究进展[J]. 遗传, 2024, 46(6): 452-465.

Zhang Yiwen, Huang Qin, Wu Yanyun, Sun Yue, Wei Yonglong. Progress on the role of LIN28A/B in tumor development and progression[J]. Hereditas(Beijing), 2024, 46(6): 452-465.

图/表 4

图1

图2

表1

LIN28A/B在人类肿瘤样本中的表达情况及临床相关性"

肿瘤类型	样本量	检测方法	临床相关性	参考文献
乳腺癌	569	TMA	1) LIN28A高、中、低表达的患者分别占1/3，高表达患者生存率显著低于中、低表达患者 2) LIN28A表达与HER2+乳腺癌相关	[52]
乳腺癌	33	IHC	1) 9/33 LIN28A上调，10/33 LIN28B上调 2) LIN28A与HER2亚型相关，LIN28B与三阴性乳腺癌相关	[15]
乳腺癌	190	IHC	83/190 LIN28B阳性，107/190 LIN28B阳性	[55]
乳腺癌	140	TMA	1) Lin28B在三阴性乳腺癌中的表达显著高于 Luminal和HER2亚型 2) Lin28B与临床肿瘤分级、远端转移、不良预后相关	[17]
结肠癌	45	IHC	19/45 LIN28A上调，14/45 LIN28B上调	[15]
结肠癌	228	TMA，IHC	LIN28B高表达与低生存率和高复发率相关	[16]
结直肠癌	595	IHC	1) 10% LIN28A阳性、8% LIN28B阳性、20% LIN28A/B阳性 2) LIN28A高表达与低生存率相关	[57]
胰腺导管腺癌	80	TMA，IHC	1) 23/80 LIN28B高表达 2) LIN28B表达与肿瘤晚期分级和不良预后相关	[58]
肝细胞癌	129	RT-qPCR	1) LIN28A在肿瘤中的表达频率显著高于正常组织 2) LIN28A高表达与不良预后相关	[59]
肝细胞癌	22	RT-qPCR	10/22 LIN28B阳性，但仅1/22 LIN28A阳性	[37]
肝细胞癌	162	RT-qPCR	60/162 LIN28B阳性	[37]
肝内胆管癌	20	IHC	3/20 LIN28B阳性，未检测到LIN28A阳性组织	[60]
胃癌	239	IHC， RT-qPCR	1) LIN28A在胃癌肿瘤和相应正常组织中均有表达，无显著差异 2) LIN28A表达与不良预后相关	[61]
胃腺癌	97	IHC	1) 42/97 LIN28B高表达，LIN28B在胃腺癌肿瘤中的表达高于相应正常组织 2) LIN28B与胃腺癌转移、TNM分期、肿瘤侵袭和分化相关	[62]
食道癌	161	IHC	1) LIN28A/B在食管癌中均存在表达上调 2) LIN28A/B高表达与淋巴结转移和不良预后相关	[63]
睾丸生殖细胞瘤	184	IHC	1) 90%以上肿瘤组织LIN28A阳性 2) LIN28A是睾丸生殖细胞瘤诊断的敏感标志物	[64]
卵巢生殖细胞瘤	121	IHC	1) 103/121 LIN28A阳性 2) LIN28A是卵巢生殖细胞瘤诊断的敏感标志物	[65]
卵巢上皮性肿瘤	211	RT-qPCR	1) 185/211 LIN28A阳性，127/211 LIN28B阳性 2) LIN28B高表达而非LIN28A与高死亡率相关	[66]
肾母细胞瘤	105	IHC	1) 18/105 LIN28B阳性，未检测到LIN28A阳性 2) LIN28B与高复发率和高死亡率相关	[9]

表1

图3

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LIN28A/B在肿瘤发生发展中的作用研究进展

Progress on the role of LIN28A/B in tumor development and progression

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