玉足海参变态附着阶段转录组分析

吴晓鹏; 黄敏伟; 陈晓瑛; 彭凯; 赵吉臣; 钟平; 刘凤坤; 张业辉; 黄文

doi:10.12131/20230105

玉足海参变态附着阶段转录组分析

doi: 10.12131/20230105

吴晓鹏^{1, 2, 3,},
黄敏伟^{2, 3, ,},
陈晓瑛^{2, 3},
彭凯^{2, 3},
赵吉臣^{2, 3},
钟平^{2, 4},
刘凤坤^{1, 2, 3},
张业辉^{3, 5},
黄文^{2, 3, ,}

1.
广东海洋大学水产学院，广东湛江 524088
2.
广东省农业科学院动物科学研究所/农业农村部华南动物营养与饲料重点实验室/广东省畜禽育种与营养研究重点实验室，广东广州 510640
3.
广东省农业科学院水产协同创新中心，广东广州 510640
4.
暨南大学生命科学学院，广东广州 510632
5.
广东省农业科学院蚕业与农产品加工研究所，广东广州 510640

基金项目: 广东省农业科学院协同创新中心课题 (水产研究中心，XT202302)；广东省基础与应用基础研究基金自然科学基金(2020A1515011115)；广东省农业科学院“青年科技骨干”人才引进项目 (R2020YJ-QG001, R2022YJ-QG001)

详细信息

作者简介:
吴晓鹏 (1996—)，男，硕士研究生，研究方向为水产动物遗传与育种。E-mail: 2012152036@qq.com

通讯作者:
黄敏伟(1991—)，男，副研究员，博士，研究方向为水产动物遗传育种与基因组学。E-mail: huangminwei@gdaas.cn

黄　文(1987—)，男，研究员，博士，研究方向为水产动物遗传与育种。E-mail: huangwen549@126.com

中图分类号: Q 953；S 917.4
计量
- 文章访问数: 65
- HTML全文浏览量: 12
- PDF下载量: 8
- 被引次数: 0
出版历程
- 收稿日期: 2023-05-19
- 修回日期: 2023-07-18
- 录用日期: 2023-07-21
- 网络出版日期: 2023-08-08

Transcriptome analysis of metamorphosis stage of Holothuria leucospilota

WU Xiaopeng^{1, 2, 3
,},
HUANG Minwei^{2, 3
, ,},
CHEN Xiaoying^{2, 3},
PENG Kai^{2, 3},
ZHAO Jichen^{2, 3},
ZHONG Ping^{2, 4},
LIU Fengkun^{1, 2, 3},
ZHANG Yehui^{3, 5},
HUANG Wen^{2, 3
, ,}

1.
College of Fisheries, Guangdong Ocean University, Zhanjiang 524088, China
2.
Institute of Animal Science, Guangdong Academy of Agricultural Sciences/Key Laboratory of Animal Nutrition and Feed Science in South China of Ministry of Agriculture and Rural Affairs/Guangdong Key Laboratory of Animal Breeding and Nutrition, Guangzhou 510640, China
3.
Collaborative Innovation Center of Aquatic Sciences, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China
4.
College of Life Science and Technology, Jinan University, Guangzhou 510632, China
5.
Sericulture & Agri-food Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China

摘要

摘要: 海参幼苗发育需要经历耳状幼体、樽形幼体、五触手幼体及幼苗阶段，而从浮游幼体变态发育至附着幼苗阶段的高死亡率是热带海参繁育中的共性问题，目前有关热带海参变态发育的调控机制仍不清楚。以玉足海参 (Holothuria leucospilota) 为研究对象，采集小耳幼体 (A)、中耳幼体 (B)、大耳幼体 (C) 和樽形幼体 (D) 4个时期样品进行高通量转录组测序分析，以探究其变态发育的分子机制。结果显示，共产生83.6 GB Raw reads，拼接获得93 528个Unigenes。对4个组测序文库的相邻组间 (A_vs_B, B_vs_C, C_vs_D) 进行两两比较，A_vs_B、B_vs_C和C_vs_D的差异表达基因数目分别为17 732、11 757和11 319 个。GO功能富集显示，差异基因主要富集于分子功能、催化活性等与细胞成长相关的GO功能。此外对KEGG通路进行了分析，结果显示差异基因显著富集于PI3K-Akt、细胞周期、癌症途径等与细胞分化增殖、凋亡相关的信号通路中，其中在幼体由浮游的大耳状幼体变态至附着的樽形幼体过程中，癌症途径的富集频率显著上升，表明其在幼体生长发育模式转换上发挥了关键作用。筛选的差异表达基因及预测的功能信息可为热带海参生长发育调控机制研究、人工繁育及分子改良应用提供参考。
- 玉足海参 /
- 转录组测序 /
- 差异基因 /
- 癌症途径
Abstract: Development of sea cucumber larvae needs to go through stages of auricularia, doliolaria, pentactula and juvenile. High mortality rate from metamorphosis and development of planktonic larvae to attachment stage of seedlings is a common problem in tropical sea cucumbers breeding. However, the gene regulation mechanism underlying the metamorphosis development of tropical sea cucumber is still unclear. In this study, we chose larval Holothuria leucospilota from four periods of early auricularia (A), mid auricularia (B), late auricularia (C) and doliolaria (D) as samples for high-throughput transcriptome sequencing to investigate the molecular mechanism underlying its metamorphosis development. The results show that a total of 83.6 GB Raw reads were generated, and 93 528 Unigenes were obtained by splicing. Pairwise comparisons between adjacent groups of the four sequencing libraries show that the number of genes with significant differential expression in A_vs_B, B_vs_C and C_vs_D were 17 732, 11 757 and 11 319, respectively. GO function enrichment shows that differential genes were mainly enriched in GO functions related to cell growth, such as molecular function and catalytic activity. In addition, KEGG pathways were analyzed, and the results show that the differential genes were significantly enriched in pathways related to cell differentiation, proliferation and apoptosis, such as PI3K-Akt, cell cycle and cancer pathways. Among them, the enrichment frequency of the pathway in cancer significantly increased during the metamorphosis process, which indicates a key role in the transformation of larval growth and development mode. The screened differentially expressed genes and predicted functional information can lay a foundation for the research on the regulatory mechanism of growth and development, artificial breeding and molecular improvement application of H. leucospilota.
- Holothuria leucospilota /
- Transcriptome sequencing /
- Differential genes /
- Pathway in cancer

HTML全文

图 1 玉足海参幼体 4 个发育时期的形态

注: a. 小耳幼体 (A期)； b. 中耳幼体 (B期)；c. 大耳幼体 (C期)；d. 樽形幼体 (D期)。

Figure 1. Morphology of H. leucospilota larva at four developmental stages

Note: a. Early auricularia (Stage A); b. Mid auricularia (Stage B); c. Late auricularia (Stage C); d. Doliolaria (Stage D).

下载: 全尺寸图片幻灯片

图 2 NR 数据库比对统计图

Figure 2. Comparison chart of NR database

下载: 全尺寸图片幻灯片

图 3 Unigene GO 功能注释结果

Figure 3. GO annotation results of unigene

下载: 全尺寸图片幻灯片

图 4 Unigene KEGG 功能注释结果

Figure 4. KEGG annotation results of unigene

下载: 全尺寸图片幻灯片

图 5 相邻组间差异表达基因火山图

注：A_vs_B. B期以A期为参照基准比较；B_vs_C. C期以B期为参照基准比较；C_vs_D. D期以C期为参照基准比较。后图同此。

Figure 5. Volcano map of differentially expressed genes between adjacent groups

Note: A_vs_B. Stage B was compared with Stage A; B_vs_C. Stage C was compared with Stage B; C_vs_D. Stage D was compared with Stage C. The same case in following figures.

下载: 全尺寸图片幻灯片

图 6 相邻组间差异表达基因 KEGG 通路分析

Figure 6. KEGG pathway analysis of differentially expressed genes between adjacent groups

下载: 全尺寸图片幻灯片

图 7 qRT-PCR 验证 RNA-seq 结果

Figure 7. RNA-Seq results verified by qRT-PCR

下载: 全尺寸图片幻灯片

表 1 引物信息

Table 1. Primer information

基因 ID　　　　 Gene ID	正向引物 Forward primer	反向引物 Reverse primer
U_57660	CACTCACGCAGAAGATGT	CCAGCAATTCCAAGTTCAAT
U_166100	CCTCATCCTTGCTGCTATT	GTCACTCCAACACCAACA
U_10254	AGTCACAGAACAGAGGTAAT	CGAACGGTCCACATATCA
U_21303	ACACCGAACACAGGAATC	CCGTTAAGGAGTAAGAGTCA
U_27749	TCATTGTTCGGATTGATTGC	AACTGCTGACATTGACCAT
U_179808	GGATGGCAAGATGAATACTG	CGTCGCTATTAAGATTAGGAG
β-Actin	GTCAGGTCATCACTATCGGCAAT	AGAGGTCTTTACGGATGTCAACGT

下载: 导出CSV

表 2 转录本组装结果统计分析

Table 2. Statistics analysis of transcript assembly results

项目类型 Item type	数量 Number
总序列数 Total sequence number	93 528
碱基总数 Total base	287 791 031
最长转录本长度 Maximum transcript length	9 920
最短转录本长度 Minimum transcript length	133
转录本平均长度 Average transcript length	3 077.06
N50 长度 N50 length	3 608
E90N50 长度 E90N50 length	3 575
GC 百分比 GC percent	38.67%
Mapped 率 Mapped percent	73.71%

下载: 导出CSV

表 3 相邻组间差异表达基因 GO 富集分析 (前 5)

Table 3. GO enrichment analysis of differentially expressed genes between adjacent groups (Top five)

相邻组间 Intergroup	GO ID	GO 分类 GO Term	频率 Frequency	P 值 P value	类型 Type
A _vs _B	GO: 0071840	细胞成分组织或生物发生 Cellular component organization or biogenesis	0.072	0.091 233
	GO: 0016043	细胞成分组织 Cellular component organization	0.068	0.303 803
	GO: 0044281	小分子代谢过程 Small molecule metabolic process	0.066	0.000 836	生物过程 Biological process
	GO: 0007017	基于微管的过程 Microtubule-based process	0.039	0.000 702
	GO: 0019752	羧酸代谢过程 Carboxylic acid metabolic process	0.037	0.000 818
	GO: 0005575	细胞组分 Cellular_component	0.661	0.081 363
	GO: 0110165	细胞解构实体 Cellular anatomical entity	0.594	0.061 953
	GO: 0005576	细胞外区 Extracellular region	0.053	0.000 702	细胞组分 Cellular component
	GO: 0042995	细胞投影 Cell projection	0.031	0.000 858
	GO: 0099080	超分子复合物 Supramolecular complex	0.030	0.001 038
	GO: 0043167	离子结合 Ion binding	0.325	0.014 108
	GO: 0016787	水解酶活性 Hydrolase activity	0.170	0.000 939
	GO: 0036094	小分子结合 Small molecule binding	0.163	0.000 962	分子功能 Molecular function
	GO: 1901265	核苷磷酸结合 Nucleoside phosphate binding	0.151	0.001 825
	GO: 0000166	核苷酸结合 Nucleotide binding	0.151	0.001 825
B_vs_C	GO: 0044281	小分子代谢过程 Small molecule metabolic process	0.063	0.097 450
	GO: 0005975	碳水化合物代谢过程 Carbohydrate metabolic process	0.030	0.000 614
	GO: 0019637	有机磷代谢过程 Organophosphate metabolic process	0.026	0.289 465	生物过程 Biological process
	GO: 0044283	小分子生物合成过程 Small molecule biosynthetic process	0.021	0.076 630
	GO: 0006091	前体代谢物和能量的产生 Generation of precursor metabolites and energy	0.018	0.011 235
	GO: 0005575	细胞组分 Cellular_component	0.676	0.001 002
	GO: 0110165	细胞解构实体 Cellular anatomical entity	0.597	0.085 132
	GO: 0031224	膜的内在成分 Intrinsic component of membrane	0.307	0.071 058	细胞组分 Cellular component
	GO: 0016021	膜的组成部分 Integral component of membrane	0.306	0.087 041
	GO: 000557 6	细胞外区 Extracellular region	0.067	0.000 566
	GO: 0043169	阳离子结合 Cation binding	0.204	0.134 971
	GO: 0046872	金属离子结合 Metal ion binding	0.204	0.121 753
	GO: 0016491	氧化还原酶活性 Oxidoreductase activity	0.090	0.002 897	分子功能 Molecular function
	GO: 0005215	转运蛋白活性 Transporter activity	0.075	0.029 888
	GO: 0005509	钙离子结合 Calcium ion binding	0.073	0.000 626
C_ vs _D	GO: 0005975	碳水化合物代谢过程 Carbohydrate metabolic process	0.025	0.162 444
	GO: 0044283	小分子生物合成过程 Small molecule biosynthetic process	0.023	0.022 217
	GO: 0007166	细胞表面受体信号通路 Cell surface receptor signaling pathway	0.022	0.113 132	生物过程 Biological process
	GO: 0006790	硫化合物代谢过程 Sulfur compound metabolic process	0.021	0.000 184
	GO: 0032259	甲基化 Methylation	0.020	0.014 144
	GO: 0031224	膜的内在成分 Intrinsic component of membrane	0.325	0.000 333
	GO: 0016021	膜的组成部分 Integral component of membrane	0.325	0.000 332
	GO: 0005576	细胞外区 Extracellular region	0.063	0.000 185	细胞组分 Cellular component
	GO: 0005581	胶原蛋白三聚体 Collagen trimer	0.031	0.000 184
	GO: 0005615	细胞外空间 Extracellular space	0.019	0.000 207
	GO: 0003674	分子功能 Molecular_function	0.820	0.000 312
	GO: 0043169	阳离子结合 Cation binding	0.214	0.000 417
	GO: 0046872	金属离子结合 Metal ion binding	0.214	0.000 382	分子功能 Molecular function
	GO: 0140096	催化活性，作用于蛋白质 Catalytic activity, acting on a protein	0.113	0.020 871
	GO: 0016491	氧化还原酶活性 Oxidoreductase activity	0.095	0.000 247

下载: 导出CSV

参考文献(46)

[1]	中国科学院中国动物志编辑委员会等. 中国动物志棘皮动物门海参纲[M]. 北京: 科学出版社, 1997: 109-110.
[2]	姚雪梅. 热带海参在我国南方沿海地区的增养殖前景[J]. 水产文摘, 2004(4): 2-5.
[3]	HUANG W, HUO D, YU Z H, et al. Spawning, larval development and juvenile growth of the tropical sea cucumber Holothuria leucospilota[J]. Aquaculture, 2018, 488: 22-29. doi: 10.1016/j.aquaculture.2018.01.013
[4]	于宗赫, 黄文, 马文刚, 等. 牟氏角毛藻和海洋红酵母对玉足海参浮游幼体发育、生长及成活率的影响[J]. 水产学报, 2021, 45(12): 2003-2010.
[5]	郑杰, 宋志远, 吴海涛, 等. 响应面法优化海参体壁自溶条件及其影响因素分析[J]. 食品安全质量检测学报, 2018, 9(22): 5981-5986.
[6]	FERGUSON C E, BENNETT N J, KOSTKA W, et al. The tragedy of the commodity is not inevitable: indigenous resistance prevents high-value fisheries collapse in the Pacific islands[J]. Global Environ Change, 2022, 73: 102477. doi: 10.1016/j.gloenvcha.2022.102477
[7]	HAWAS U W, ABOU EL-KASSEM L T, SHAHER F M, et al. Sulfated triterpene glycosides from the Saudi Red Sea cucumber Holothuria atra with antioxidant and cytotoxic activities[J]. Thalassas: An Int J Mar Sci, 2021, 37(2): 817-824. doi: 10.1007/s41208-021-00305-4
[8]	ZHAO Y C, XUE C H, ZHANG T T, et al. Saponins from sea cucumber and their biological activities[J]. J Agric Food Chem, 2018, 66(28): 7222-7237. doi: 10.1021/acs.jafc.8b01770
[9]	LU Z Q, SUN N, DONG L, et al. Production of bioactive peptides from sea cucumber and its potential health benefits: a comprehensive review[J]. J Agric Food Chem, 2022, 70(25): 7607-7625. doi: 10.1021/acs.jafc.2c02696
[10]	LI C L, ZHAO W, QIN C X, et al. Comparative transcriptome analysis reveals changes in gene expression in sea cucumber (Holothuria leucospilota)in response to acute temperature stress[J]. Comp Biochem Physiol D, 2021, 40: 100883.
[11]	PURCELL S W, MERCIER A, CONAND C, et al. Sea cucumber fisheries: global analysis of stocks, management measures and drivers of overfishing[J]. Fish Fish, 2013, 14(1): 34-59. doi: 10.1111/j.1467-2979.2011.00443.x
[12]	谭春明, 赵旺, 马振华, 等. 红腹海参消化道指标、组织学和酶活性的季节变化[J]. 南方水产科学, 2022, 18(5): 39-45.
[13]	RAKAJ A, FIANCHINI A, BONCAGNI P, et al. Spawning and rearing of Holothuria tubulosa: a new candidate for aquaculture in the Mediterranean region[J]. Aquac Res, 2018, 49(1): 557-568. doi: 10.1111/are.13487
[14]	RAKAJ A, FIANCHINI A, BONCAGNI P, et al. Artificial reproduction of Holothuria polii: a new candidate for aquaculture[J]. Aquaculture, 2019, 498: 444-453. doi: 10.1016/j.aquaculture.2018.08.060
[15]	HU C Q, LI H P, XIA J J, et al. Spawning, larval development and juvenile growth of the sea cucumber Stichopus horrens[J]. Aquaculture, 2013, 404: 47-54.
[16]	冯永勤, 翁文明, 方再光, 等. 糙海参苗种规模化繁育技术研究[J]. 水产科学, 2021, 40(5): 750-756.
[17]	黄星美, 赵旺, 李长林, 等. 盐度对玉足海参浮游幼体生长的影响[J]. 南方水产科学, 2022, 18(3): 111-117.
[18]	宋汝浩, 胡瑞芹, 李根芳, 等. 基于转录组学技术对斑马鱼肝脏组织低氧胁迫影响的研究[J]. 南方水产科学, 2022, 18(6): 60-68.
[19]	ZHAO J C, CHEN X Y, HE Z H, et al. Transcriptome analysis provides new insights into host response to Hepatopancreatic necrosis disease in the black tiger shrimp Penaeus monodon[J]. J Ocean Univ China, 2021, 20: 1183-1194. doi: 10.1007/s11802-021-4744-x
[20]	范嗣刚, 杨文燕, 黄皓, 等. 不同生长速率花鲈肌肉转录组分析及生长相关基因筛选[J]. 广东海洋大学学报, 2022, 42(5): 9-17.
[21]	LIN X Y, DENG S Z, LIU X D, et al. Comparative transcriptome analysis of Phascolosoma esculenta under different salinities[J]. Aquac Fish, 2020, 5(6): 323-330. doi: 10.1016/j.aaf.2020.06.013
[22]	BYRNE M, KOOP D, STRBENAC D, et al. Transcriptomic analysis of sea star development through metamorphosis to the highly derived pentameral body plan with a focus on neural transcription factors[J]. DNA Res, 2020, 27(1): dsaa007. doi: 10.1093/dnares/dsaa007
[23]	CONACO C, NEVEU P, ZHOU H J, et al. Transcriptome profiling of the demosponge Amphimedon queenslandica reveals genomewide events that accompany major life cycle transitions[J]. BMC Genomics, 2012, 13: 1-19. doi: 10.1186/1471-2164-13-1
[24]	BORAH B K, HAUZEL L, RENTHLEI Z, et al. Photic and non-photic regulation of growth, development, and metamorphosis in giant tree frog (Rhacophorus maximus) tadpoles[J]. Biol Rhythm Res, 2018, 49(6): 955-967.
[25]	HODIN J, HEYLAND A, MERCIER A, et al. Culturing echinoderm larvae through metamorphosis[J]. Methods Cell Biol, 2019, 150: 125-169.
[26]	陈雪峰, 王春琳, 顾志敏, 等. 罗氏沼虾(Macrobrachium rosenbergii)卵巢发育不同时期转录组分析[J]. 海洋与湖沼, 2019, 50(2): 398-408.
[27]	YIN J Y, LI Z B, PAN C H, et al. Understanding the internal differences behind unsynchronized growth in sea cucumber Holothuria leucospilota by integration of transcriptomic and metabolomic data[J]. Aquac Rep, 2023, 32: 101688.
[28]	ZAKERI Z, LOCKSHIN R A. Cell death during development[J]. J Immunol Methods, 2002, 265(1/2): 3-20.
[29]	NANUT M P, FONOVIĆ U P, JAKOŠ T, et al. The role of cysteine peptidases in hematopoietic stem cell differentiation and modulation of immune system function[J]. Front Immunol, 2021, 12: 680279. doi: 10.3389/fimmu.2021.680279
[30]	XIE J, SUN Y, CAO Y, et al. Transcriptomic and metabolomic analyses provide insights into the growth and development advantages of triploid Apostichopus japonicus[J]. Mar Biotechnol, 2022, 24(1): 151-162. doi: 10.1007/s10126-022-10093-4
[31]	ASADI M, TAGHIZADEH S, KAVIANI E, et al. Caspase-3: structure, function, and biotechnological aspects[J]. Biotechnol Appl Biochem, 2022, 69(4): 1633-1645. doi: 10.1002/bab.2233
[32]	MCCOMB S, CHAN P K, GUINOT A, et al. Efficient apoptosis requires feedback amplification of upstream apoptotic signals by effector caspase-3 or-7[J]. Sci Adv, 2019, 5(7): eaau9433. doi: 10.1126/sciadv.aau9433
[33]	CHAMBON J P, SOULE J, POMIES P, et al. Tail regression in Ciona intestinalis (Prochordate) involves a caspase-dependent apoptosis event associated with ERK activation[J]. Development, 2002, 129(13): 3105-3114.
[34]	AIELLO D, PATEL K, LASAGNA E. The myostatin gene: an overview of mechanisms of action and its relevance to livestock animals[J]. Anim Genet, 2018, 49(6): 505-519. doi: 10.1111/age.12696
[35]	HOOGAARS W M H, JASPERS R T. Past, present, and future perspective of targeting myostatin and related signaling pathways to counteract muscle atrophy[J]. Muscle Atrophy, 2018, 1088: 153-206.
[36]	杨慧荣, 曾泽乾, 杨炎, 等. 鱼类肌肉生长抑制素myostatin研究进展[J]. 中山大学学报(自然科学版)(中英文), 2022, 61(5): 1-8.
[37]	陈素华, 吴杨平, 陈爱华, 等. 文蛤CDK1基因在选育与自然群体早期生长阶段中的表达特征[J]. 中国水产科学, 2020, 27(9): 1042-1051.
[38]	MOMOSE T, DERELLE R, HOULISTON E. A maternally localised Wnt ligand required for axial patterning in the cnidarian Clytia hemisphaerica[J]. Development, 2008, 135: 2105-2113. doi: 10.1242/dev.021543
[39]	TEO R, MÖHRLEN F, PLICKERT G, et al. An evolutionary conserved role of Wnt signaling in stem cell fate decision[J]. Dev Biol, 2006, 289(1): 91-99. doi: 10.1016/j.ydbio.2005.10.009
[40]	江红霞, 刘慧芬, 马晓, 等. 转录组测序筛选克氏原螯虾卵巢发育、免疫和生长相关基因[J]. 水产学报, 2021, 45(3): 396-414.
[41]	JERE S W, HOURELD N N, ABRAHAMSE H. Role of the PI3K/AKT (mTOR and GSK3β) signalling pathway and photobiomodulation in dia-betic wound healing[J]. Cytokine & Growth Factor Rev, 2019, 50: 52-59.
[42]	TANG B L. Neuroprotection by glucose-6-phosphate dehydrogenase and the pentose phosphate pathway[J]. J Cell Biochem, 2019, 120(9): 14285-14295.
[43]	丁丹, 潘宝平, 王玉梅, 等. 青蛤 (Cyclina sinensis) AP-1基因的克隆及在鳗弧菌 (Vibrio anguillarum) 侵染下的表达分析[J]. 海洋与湖沼, 2018, 49(1): 192-197.
[44]	BACKES T M, RÖSSLER O G, HUI X, et al. Stimulation of TRPV1 channels activates the AP-1 transcription factor[J]. Biochem Pharmacol, 2018, 150: 160-169. doi: 10.1016/j.bcp.2018.02.008
[45]	马清花, 陈雪妍, 卫唯, 等. 青海湖裸鲤AP-1基因的克隆与表达分析[J]. 基因组学与应用生物学, 2020, 39(7): 2964-2971.
[46]	CHEUNG C H A, CHANG Y C, LIN T Y, et al. Anti-apoptotic proteins in the autophagic world: an update on functions of XIAP, Survivin, and BRUCE[J]. J Biomed Sci, 2020, 27(1): 1-10. doi: 10.1186/s12929-019-0592-z