1p缺失在多发性骨髓瘤中的研究进展
Research Progress of 1p Deletion in Multiple Myeloma
DOI: 10.12677/ACM.2023.1361267, PDF, HTML, XML, 下载: 383  浏览: 552  国家自然科学基金支持
作者: 郭 沙*, 龚 珊, 张 瑞, 曲建华#:新疆医科大学第一附属医院,新疆 乌鲁木齐
关键词: 多发性骨髓瘤1p缺失发病机制Multiple Myeloma 1p Deletion Pathogenesis
摘要: 多发性骨髓瘤(MM)是终末分化的B细胞恶性肿瘤,被广泛认为是无法治愈的,因为许多患者要么产生了耐药性,要么最终复发。为了制定精确有效的治疗策略,我们必须了解MM的发病机制。在本综述中,我们描述了一些肿瘤抑制因子在1p缺失中丢失或下调,总结了它们的生物学功能及其在MM发病机制中的作用,希望发现潜在的治疗靶点,促进未来治疗方法的发展。
Abstract: Multiple myeloma (MM) is a terminally differentiated B-cell malignancy that is widely considered incurable because many patients either develop drug resistance or eventually relapse. In order to develop accurate and effective treatment strategies, we must understand the pathogenesis of MM. In this review, we describe the loss or down-regulation of some tumor suppressors in 1p deletion, summarize their biological functions and their roles in the pathogenesis of MM, and hope to find potential therapeutic targets and promote the development of future treatment methods.
文章引用:郭沙, 龚珊, 张瑞, 曲建华. 1p缺失在多发性骨髓瘤中的研究进展[J]. 临床医学进展, 2023, 13(6): 9053-9059. https://doi.org/10.12677/ACM.2023.1361267

1. 引言

多发性骨髓瘤(multiple myeloma, MM)是单克隆的浆细胞异常增生所致的恶性疾病,暂无法治愈 [1] 。MM占所有癌症的1%,约占所有血液系统恶性肿瘤的10% [2] 。在过去的二十多年,患者的生存率有了实质性的改善 [3] 。MM具有显著的生物学和遗传异质性,其特征是具有额外的染色体拷贝(或超二倍体)或与免疫球蛋白重链(IgH)基因所在的14号染色体相关的易位,但预后的改善主要是由针对浆细胞生物学关键组成部分的治疗方案所推动,而不是潜在的基因组异常 [4] 。例如蛋白酶体抑制剂硼替唑米可以靶向DNA修复通路和/或NF-κB激活,同时靶向癌症生物学和正常浆细胞生物学。

基因组和表观基因组图谱揭示了异质性和复杂的基线状态,而进一步的克隆进化推动了MM的进展和复发。基因组不稳定性是MM中复杂基因组现象的驱动因素之一,这种复杂性通常会导致细胞分裂过程中的基因组改变,例如染色体不稳定(chromosomal instability, CIN),微卫星不稳定和突变频率增加 [5] 。在这些改变中,CIN通常会导致染色体拷贝数和结构变化,根据在不同MM阶段检测到的时间线 [6] ,分为原发性遗传事件和次级遗传事件。在MGUS阶段检测到的遗传事件可能是原发事件;在MM阶段存在而在MGUS中不存在的可能是继发事件 [7] 。MM是导致肿瘤进展的原发性事件,继发事件和明显的克隆异质性的组合。主要基因组事件的特征通常是获得影响IGH基因的超二倍体或易位,次要基因组事件包括染色体易位(copy number variations, CNVs),单核苷酸变异。

1号染色体不稳定性是参与MM发病机制最常见的拷贝数变异CNV和结构变化,它通常会导致整个染色体臂和扩增或缺失的间质短区域的DNA获得和丢失 [8] 。全臂水平畸变通常与高危骨髓瘤有关,最常见的是同染色体的形成,导致单臂重复和相对染色体臂丢失。已经描述了涉及1号染色体短臂和长臂的各种异常,包括1q增益、1p缺失以及平衡或跳跃易位 [8] 。

染色体1p缺失通常与MM的不良预后相关,包括间质缺失、全臂缺失、拷贝数中性杂合性丢失(loss of heterozygosity, LOH)、完全或部分单亲二倍体(uniparental disomy, UPD)。这些区域中某些基因的表达降低被认为与不良预后相关。除了1p12,1p22.1-1p21.3,1p31和1p32这四个区域,1p36上的p73也被认为是MM的治疗靶点。

2. 1p12

1p12的参与被认为是MM的不良预后因素 [9] 。通过进行基因定位、基因表达、FISH和突变分析,发现该区域具有序列相似性的46家族C (FAM46C) (又名末端转核苷酰酶5C (TENT5C))基于其复发性纯合性缺失和突变在MM中具有致病性和预后意义 [10] 。有趣的是,上述缺失和突变在其他癌症中很少被发现 [11] 。FAM46C作为真核生物非经典poly (A)聚合酶,可以增强mRNA稳定性和基因表达 [12] 。在多发性骨髓瘤中,FAM46C与纤连蛋白Ⅲ型结构域3A (Fibronectin Type III Domain Containing 3A, FNDC3A)形成肿瘤抑制复合物 [13] 。该复合物在MM细胞中具有细胞毒性,通过损害自噬,引起蛋白质的积累、聚集和凋亡 [14] 。FAM46C的缺失通过激活PI3K-Akt通路促进肿瘤发生,该通路还激活ERK和抗凋亡信号,并赋予地塞米松和来那度胺治疗的相对抗性 [15] 。过表达FAM46C下调干扰素调节因子4 (IRF4)、CCAAT增强子结合蛋白β (CEBPB)和MYC,同时上调免疫球蛋白(Ig)轻链。

热休克蛋白家族A (Hsp70)成员5 (HSPA5)/BIP在MM细胞中诱导大量毒性。在MM细胞系中重新引入FAM46C可以诱导多聚腺苷酸化引起的细胞死亡,同时稳定那些编码内质网靶向蛋白的mRNA,因此成为MM的一个有趣的靶点。

3. 1p22.1-1p21.3

1p22.1-1p21.3被认为是1p上最常见的缺失区域,金属应答元件结合转录因子2 (MTF2)、跨膜转运蛋白5 (TMED5)、核糖体蛋白L5 (RPL5)和嗜生态病毒整合位点5 (EVI5)被鉴定为该区域的下调基因。Mtf2是一种多梳状蛋白,可以有意识地招募多梳抑制复合体2 (PRC2)到基因组靶点,并被报道具有癌基因和抑癌基因的双重功能 [16] [17] 。然而,尽管MTF2的表达下调与MM的总生存期(overall survival, OS)或无进展生存期(progression free survival, PFS)受损无关,但TMED5的低表达与短生存期弱相关,并且在这两个基因中都没有发现突变。TMED5是Wnt相关的高尔基体信号基因,可被MIR-G-1上调 [18] 。它通过与Wnt家族成员7B (WNT7B)相互作用促进宫颈癌细胞增殖、迁移、侵袭和EMT进程,从而激活经典的WNT-CTNNB1/β-catenin信号通路 [19] 。以上研究表明TMED5是一个候选癌基因。因此,研究TMED5表达降低与MM患者短期生存的关系是很有意义的。

更多的关注EVI5和RPL5在MM发病和药物反应中的表达下调,mRNA表达降低与诊断病例中更差的生存相关。这两个基因的失活可能是MM进展的驱动因素 [20] 。EVI5调节胞质分裂、细胞周期进程、细胞膜运输。除MM外,EVI5在泛癌症项目中被报道为癌基因,调节细胞周期蛋白积累和细胞分裂 [21] 。EVI5的缺失如何与更差的生存和MM进展相关仍不确定。RPL5是核糖体的一个组成部分,核糖体是一个大的核糖核蛋白复合体,负责细胞内蛋白质的合成 [22] 。RPL5是泛癌症项目中的一个复发性突变基因 [23] 。在20%~40%的突变频率较低的MM患者中,RPL5缺失 [24] 。RPL5的mRNA表达作为硼替佐米初始反应的生物标志物,在硼替佐米初始反应的复发患者中显著降低。将硼替佐米纳入治疗时,RPL5低的患者具有更好的PFS [25] 。

4. 1p31

1p31.3包含14个基因。泛素特异性肽酶33 (USP33),最早被鉴定为一种冯·希佩尔–林道(VHL)肿瘤抑制蛋白相互作用的去泛素化酶,被发现在该区域低表达 [26] 。USP33在多种细胞过程中发挥关键作用。例如,USP33与USP20共同调控细胞表面β2AR信号的内吞后分选和强度;USP33对中心体稳态也至关重要,因为它调节CP110的表达 [27] 。USP33的消融被发现通过破坏CP110的稳定性来抑制中心体扩增和有丝分裂缺陷 [28] ;USP33还可以去泛素化RalB促进自噬体形成,这有助于区分Ral B在自噬和先天免疫反应中的功能 [29] 。

定位于1p31.1的MutS蛋白同源物4 (MSH4)和Disabled 1 (DAB1)的表达随着1p31的缺失而降低 [30] 。MSH4是Mut H同源基因家族的一员,其表达仅限于减数分裂组织,在减数分裂时同源染色体的相互重组和正确分离是必需的。由于MSH4参与DNA修复,MSH4可能导致癌症中的DNA不稳定性 [31] 。DAB1是果蝇致残位点的人类同源基因之一;在哺乳动物中,它参与发育中大脑皮层神经元的迁移和分层。DAB1是一个大的常见脆性位点基因,在多种癌症中失活,因此暗示其作为肿瘤抑制因子的作用 [32] 。

尚未有研究对上述基因在MM中的作用进行研究,需要进一步分析。

5. 1p32

提示1p32的缺失是年轻MM患者的主要独立预后因素。1p32.3处的细胞周期蛋白依赖性激酶抑制因子2C (CDKN2C)和Fas相关因子1 (FAF1)是鉴定到的受1p纯合缺失影响的2个基因 [33] [34] 。CDKN2C又称p18INK4c,是一种D型细胞周期蛋白依赖性激酶(CDK)抑制剂。CDKN2C通过抑制Cdk4/Cdk6,在产生非周期分泌免疫球蛋白(Ig)的浆细胞(PCs)中发挥重要作用,从而控制PC稳态 [35] 。在晚期B细胞终末分化过程中,它在控制细胞周期阻滞和细胞死亡方面也发挥着重要作用 [36] 。在大约40%的MM细胞系中发现CDKN2C的缺失,通过控制G1-S转换点与增殖增加有关 [37] 。CDKN2C纯合或半合子缺失通常具有更差的OS,表明其在MM进展中作为肿瘤抑制因子的作用 [38] 。FAF1是一种泛素结合蛋白,也是DNA复制叉进展所必需的 [39] 。FAF1被报道与Fas诱导的细胞杀伤相关,并增强Fas介导的细胞凋亡 [40] 。在泛癌症研究中,它被认为是一种肿瘤抑制因子,因为它调节细胞凋亡和NF-κB活性,以及泛素化和蛋白酶体降解以及FAF1的丢失,这可能导致肿瘤发生的多个方面 [41] 。此外,FAF1的缺失与TGF-β3的表达呈显著负相关,后者被报道在晚期癌症中过度激活 [42] 。FAF1的缺失被报道与MM的不良OS相关,但其发挥的确切作用值得进一步探索。

6. 1p35-1p36

p73基因定位于1p36.32,是1997年发现的p53肿瘤抑制因子的同源基因。p73和Tp53的DNA结合域(DBD)具有79%的氨基酸一致性。两种蛋白都能结合相同的DNA序列并反式激活相同的启动子。p73能够编码具有转录活性的p73 (TAp73)异构体,这些异构体含有一个反式激活结构域(TA),以及具有较短的氨基末端缺乏TA结构域的显性负调控ΔNp73转录异构体。TAP73产物发挥类似p53的功能,而ΔNp73产物则完全相反。TAp73全长变异体通过激活细胞或病毒致癌基因、特异性DNA损伤等诱导细胞凋亡。p53和TAp73可以诱导ΔNp73异构体的表达,后者形成一个显性负反馈环路来调节前者。TAp73和ΔNp73之间的平衡调节细胞对程序性细胞死亡的敏感性 [43] 。在MM中,虽然p73的缺失鲜有报道,但高达21%的患者中可见p73的高甲基化,导致其表达沉默,观察到罕见突变 [44] 。对小分子的治疗作用进行了研究。PRIMA-1Met/APR-246在MM中,PRIMA-1Met可以诱导MM细胞凋亡,抑制MM细胞的克隆形成和迁移。这种作用不是p53依赖的,而是部分p73依赖的,它诱导p73的激活,上调Noxa,下调MCL-1 [45] 。因此,p73在MM发病机制中的作用以及能否作为治疗靶点主要取决于其异构体。p73全长可能发挥抑癌作用,截短异构体可能发挥致癌作用。

7. 小结

我们描述了染色体1p的缺失的生物学功能以及它们在MM中的病理作用。导致各种肿瘤抑制基因的缺失或下调,如MTF2、USP33、MSH4和DAB1,在减数分裂、中心体稳态、神经发育等的调控中具有生物学意义。通过研究这些基因功能,我们可以更好地了解MM的发病机制,发现新的治疗靶点,并启发未来治疗方法的发展。

基金项目

国家自然科学基金资助项目(项目编号:8216010085);新疆维吾尔自治区天山青年创新团队(项目编号:2022D14008)。

NOTES

*第一作者。

#通讯作者。

参考文献

[1] 中国医师协会血液科医师分会, 中华医学会血液学分会. 中国多发性骨髓瘤诊治指南(2022年修订) [J]. 中华内科杂志, 2022, 61(5): 480-487.
[2] Rajkumar, S.V. (2022) Multiple Myeloma: 2022 Update on Diagnosis, Risk Strati-fication, and Management. American Journal of Hematology, 97, 1086-1107.
https://doi.org/10.1002/ajh.26590
[3] Silberstein, J., Tuchman, S. and Grant, S.J. (2022) What Is Multiple Mye-loma? JAMA, 327, 497.
https://doi.org/10.1001/jama.2021.25306
[4] Boise, L.H., Kaufman, J.L., Bahlis, N.J., et al. (2014) The Tao of Myeloma. Blood, 124, 1873-1879.
https://doi.org/10.1182/blood-2014-05-578732
[5] Luo, S., Su, T., Zhou, X., et al. (2022) Chromosome 1 Insta-bility in Multiple Myeloma: Aberrant Gene Expression, Pathogenesis, and Potential Therapeutic Target. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 36, e22341.
https://doi.org/10.1096/fj.202200354
[6] Neuse, C.J., Lomas, O.C., Schliemann, C., et al. (2020) Genome Insta-bility in Multiple Myeloma. Leukemia, 34, 2887-2897.
https://doi.org/10.1038/s41375-020-0921-y
[7] Hultcrantz, M., Yellapantula, V. and Rustad, E.H. (2020) Ge-nomic Profiling of Multiple Myeloma: New Insights and Modern Technologies. Best Practice & Research Clinical Haematology, 33, Article ID: 101153.
https://doi.org/10.1016/j.beha.2020.101153
[8] Giri, S., Huntington, S.F., Wang, R., et al. (2020) Chromosome 1 Abnormalities and Survival of Patients with Multiple Myeloma in the Era of Novel Agents. Blood Advances, 4, 2245-2253.
https://doi.org/10.1182/bloodadvances.2019001425
[9] Panani, A.D., Ferti, A.D., Papaxoinis, C., et al. (2004) Cytogenetic Data as a Prognostic Factor in Multiple Myeloma Patients: Involvement of 1p12 Region an Adverse Prog-nostic Factor. Anticancer Research, 24, 4141-4146.
[10] Boyd, K.D., Ross, F.M., Walker, B.A., et al. (2011) Mapping of Chromosome 1p Deletions in Myeloma Identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as Being Genes in Re-gions Associated with Adverse Survival. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 17, 7776-7784.
https://doi.org/10.1158/1078-0432.CCR-11-1791
[11] Lohr, J.G., Stojanov, P., Carter, S.L., et al. (2014) Wide-spread Genetic Heterogeneity in Multiple Myeloma: Implications for Targeted Therapy. Cancer Cell, 25, 91-101.
https://doi.org/10.1016/j.ccr.2013.12.015
[12] Liu, S., Chen, H., Yin, Y., et al. (2023) Inhibition of FAM46/TENT5 Activity by BCCIPα Adopting a Unique Fold. Science Advances, 9, eadf5583.
https://doi.org/10.1126/sciadv.adf5583
[13] Zhang, H., Zhang, S.-H., Hu, J.-L., et al. (2021) Structural and Func-tional Characterization of Multiple Myeloma Associated Cytoplasmic poly(A) Polymerase FAM46C. Cancer Communi-cations (London, England), 41, 615-630.
https://doi.org/10.1002/cac2.12163
[14] Manfrini, N., Mancino, M., Miluzio, A., et al. (2020) FAM46C and FNDC3A Are Multiple Myeloma Tumor Suppressors That Act in Concert to Impair Clearing of Protein Aggregates and Autophagy. Cancer Research, 80, 4693-4706.
https://doi.org/10.1158/0008-5472.CAN-20-1357
[15] Kanasugi, J., Hanamura, I., Ota, A., et al. (2020) Biallelic Loss of FAM46C Triggers Tumor Growth with Concomitant Activation of Akt Signaling in Multiple Myeloma Cells. Cancer Science, 111, 1663-1675.
https://doi.org/10.1111/cas.14386
[16] Comet, I., Riising, E.M., Leblanc, B., et al. (2016) Maintaining Cell Identity: PRC2-Mediated Regulation of Transcription and Cancer. Nature Reviews. Cancer, 16, 803-810.
https://doi.org/10.1038/nrc.2016.83
[17] Perino, M., van Mierlo, G., Karemaker, I.D., et al. (2018) MTF2 Recruits Polycomb Repressive Complex 2 by Helical-Shape-Selective DNA Binding. Nature Genetics, 50, 1002-1010.
https://doi.org/10.1038/s41588-018-0134-8
[18] Saul, M.C., Majdak, P., Perez, S., et al. (2017) High Motivation for Exercise Is Associated with Altered Chromatin Regulators of Monoamine Receptor Gene Expression in the Striatum of Selectively Bred Mice. Genes, Brain, and Behavior, 16, 328-341.
https://doi.org/10.1111/gbb.12347
[19] Yang, Z., Sun, Q., Guo, J., et al. (2019) GRSF1-Mediated MIR-G-1 Promotes Malignant Behavior and Nuclear Autophagy by Directly Upregulating TMED5 and LMNB1 in Cervical Cancer Cells. Autophagy, 15, 668-685.
https://doi.org/10.1080/15548627.2018.1539590
[20] Liu, Y., Yu, H., Yoo, S., et al. (2019) A Network Analysis of Multiple Myeloma Related Gene Signatures. Cancers, 11, 1452.
https://doi.org/10.3390/cancers11101452
[21] Yan, M., Niu, L., Liu, J., et al. (2021) circEVI5 Acts as a miR-4793-3p Sponge to Suppress the Proliferation of Gastric Cancer. Cell Death & Disease, 12, 774.
https://doi.org/10.1038/s41419-021-04061-4
[22] Małecki, J.M., Odonohue, M.-F., Kim, Y., et al. (2021) Human METTL18 Is a Histidine-Specific Methyltransferase That Targets RPL3 and Affects Ribosome Biogenesis and Function. Nucleic Acids Research, 49, 3185-3203.
https://doi.org/10.1093/nar/gkab088
[23] ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium (2023) Author Correction: Pan-Cancer Analysis of Whole Genomes. Nature, 614, E39.
[24] Hofman, I.J.F., Patchett, S., van Duin, M., et al. (2017) Low Frequency Mutations in Ribosomal Proteins RPL10 and RPL5 in Multiple Myeloma. Haematologica, 102, e317-e320.
https://doi.org/10.3324/haematol.2016.162198
[25] Hofman, I.J.F., van Duin, M., Bruyne, E., et al. (2017) RPL5 on 1p22.1 Is Recurrently Deleted in Multiple Myeloma and Its Expression Is Linked to Bortezomib Response. Leukemia, 31, 1706-1714.
https://doi.org/10.1038/leu.2016.370
[26] Zhang, A., Huang, Z., Tao, W., et al. (2022) USP33 Deubiquitinates and Stabilizes HIF-2alpha to Promote Hypoxia Response in Glioma Stem Cells. The EMBO Journal, 41, e109187.
https://doi.org/10.15252/embj.2021109187
[27] Kitamura, H. (2023) Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders. International Journal of Molecular Sciences, 24, 3219.
https://doi.org/10.3390/ijms24043219
[28] Chen, S., Liang, Y., Shen, Y., et al. (2023) lncRNA XIST/miR-129-2-3p Axis Targets CCP110 to Regulate the Proliferation, Invasion and Migration of Endometrial Cancer Cells. Experimental and Therapeutic Medicine, 25, Article No. 159.
https://doi.org/10.3892/etm.2023.11858
[29] Simicek, M., Lievens, S., Laga, M., et al. (2013) The Deubiquitylase USP33 Discriminates between RALB Functions in Autophagy and Innate Immune Response. Nature Cell Biology, 15, 1220-1230.
https://doi.org/10.1038/ncb2847
[30] Chng, W.J., Gertz, M.A., Chung, T.-H., et al. (2010) Correlation between Array-Comparative Genomic Hybridization-Defined Genomic Gains and Losses and Survival: Identification of 1p31-32 Deletion as a Prognostic Factor in Myeloma. Leukemia, 24, 833-842.
https://doi.org/10.1038/leu.2010.21
[31] Clark, N., Wu, X. and Her, C. (2013) MutS Homologues hMSH4 and hMSH5: Genetic Variations, Functions, and Implications in Human Diseases. Current Genomics, 14, 81-90.
https://doi.org/10.2174/1389202911314020002
[32] Li, L., Hao, J., Yan, C.-Q., et al. (2020) Inhibition of mi-croRNA-300 Inhibits Cell Adhesion, Migration, and Invasion of Prostate Cancer Cells by Promoting the Expression of DAB1. Cell Cycle (Georgetown, Tex.), 19, 2793-2810.
https://doi.org/10.1080/15384101.2020.1823730
[33] Wang, H., Meng, H., Wang, J., et al. (2020) Clinical Char-acteristics and Prognostic Values of 1p32.3 Deletion Detected through Fluorescence in Situ Hybridization in Patients with Newly Diagnosed Multiple Myeloma: A Single-Center Study in China. Frontiers of Medicine, 14, 327-334.
https://doi.org/10.1007/s11684-019-0712-x
[34] Hebraud, B., Leleu, X., Lauwers-Cances, V., et al. (2014) Dele-tion of the 1p32 Region Is a Major Independent Prognostic Factor in Young Patients with Myeloma: The IFM Experi-ence on 1195 Patients. Leukemia, 28, 675-679.
https://doi.org/10.1038/leu.2013.225
[35] Bretz, J., Garcia, J., Huang, X., et al. (2011) Noxa Mediates p18INK4c Cell-Cycle Control of Homeostasis in B Cells and Plasma Cell Precursors. Blood, 117, 2179-2188.
https://doi.org/10.1182/blood-2010-06-288027
[36] Morse, L., Chen, D., Franklin, D., et al. (1997) Induction of Cell Cycle Arrest and B Cell Terminal Differentiation by CDK Inhibitor p18(INK4c) and IL-6. Immunity, 6, 47-56.
https://doi.org/10.1016/S1074-7613(00)80241-1
[37] Kulkarni, M.S., Daggett, J.L., Bender, T.P., et al. (2002) Frequent Inactivation of the Cyclin-Dependent Kinase Inhibitor p18 by Homozygous Deletion in Multiple Myeloma Cell Lines: Ectopic p18 Expression Inhibits Growth and Induces Apoptosis. Leukemia, 16, 127-134.
https://doi.org/10.1038/sj.leu.2402328
[38] Adamia, S., Bhatt, S., Wen, K., et al. (2022) Combination Therapy Targeting Erk1/2 and CDK4/6i in Relapsed Refractory Multiple Myeloma. Leukemia, 36, 1088-1101.
https://doi.org/10.1038/s41375-021-01475-z
[39] Franz, A., Pirson, P.A., Pilger, D., et al. (2016) Chroma-tin-Associated Degradation Is Defined by UBXN-3/FAF1 to Safeguard DNA Replication Fork Progression. Nature Communications, 7, Article No. 10612.
https://doi.org/10.1038/ncomms10612
[40] Li, Y., Wu, X., Li, J., et al. (2022) Circ_0004354 Might Compete with Circ_0040039 to Induce NPCs Death and Inflammatory Response by Targeting miR-345-3p-FAF1/TP73 Axis in Inter-vertebral Disc Degeneration. Oxidative Medicine and Cellular Longevity, 2022, Article ID: 2776440.
https://doi.org/10.1155/2022/2776440
[41] Song, S., Park, J.K., Shin, S.C., et al. (2022) The Complex of Fas-Associated Factor 1 with Hsp70 Stabilizes the Adherens Junction Integrity by Suppressing RhoA Activation. Jour-nal of Molecular Cell Biology, 14, mjac037.
https://doi.org/10.1093/jmcb/mjac037
[42] Xie, F., Jin, K., Shao, L., et al. (2017) FAF1 Phosphorylation by AKT Accumulates TGF-β Type II Receptor and Drives Breast Cancer Metastasis. Nature Communications, 8, Article No. 15021.
https://doi.org/10.1038/ncomms15021
[43] Omran, Z., Dalhat, M., Abdullah, O., et al. (2021) Targeting Post-Translational Modifications of the p73 Protein: A Promising Therapeutic Strategy for Tumors. Cancers, 13, 1916.
https://doi.org/10.3390/cancers13081916
[44] Schultheis, B., Krämer, A., Willer, A., et al. (1999) Analysis of p73 and p53 Gene Deletions in Multiple Myeloma. Leukemia, 13, 2099-2103.
https://pubmed.ncbi.nlm.nih.gov/10602435
https://doi.org/10.1038/sj.leu.2401609
[45] Saha, M.N., Jiang, H., Yang, Y., Reece, D. and Chang, H. (2018) Correction: PRIMA-1Met/APR-246 Displays High Antitumor Activity in Multiple Myeloma by Induction of p73 and Noxa. Molecular Cancer Therapeutics, 17, 1143.
https://pubmed.ncbi.nlm.nih.gov/29717080
https://doi.org/10.1158/1535-7163.MCT-18-0096