Expression and bioinformatics analysis of hsa-miR-34a in tumors

doi:10.3969/j.issn.1673-8640.2022.07.012

Abstract

Abstract:

Objective To analyze the expression of homo sapiens microRNA（miR）-34a（hsa-miR-34a） in different tumors,to predict its target genes,and to analyze its biological function and mechanism. Methods Sequence was obtained from miRBase database to analyze the position of hsa-miR-34a in human genome and its conservation among species. TargetScan,miRWalk,miRDB and mirDIP were used to predict the target gene set of hsa-miR-34a and take the intersection,the expression of which in different human tissues was analyzed through TiGER database. Gene Ontology（GO） enrichment analysis and REACTOME signaling pathway enrichment analysis of hsa-miR-34a target genes were performed using PANTHER and DAVID online tools. The interaction network of hsa-miR-34a target genes corresponding to target proteins was constructed by STRING database. Results The expressions of hsa-miR-34a in breast cancer,prostate cancer,bladder cancer and other tumors were decreased. The sequence encoding hsa-miR-34a was highly conserved among different species. A total of 225 target genes were obtained,and the top 30 target genes were selected after Target Score functional sequencing. There was no statistical significance in the relative expression of target genes among different human tissues（P>0.05）. GO enrichment analysis showed that hsa-miR-34a target genes were mainly expressed in clathrin vesicles,vesicle membranes and their material transport,multicellular biological processes and development,neurogenesis and development,anatomical structure development and so on. REACTOME signaling pathway enrichment analysis showed that hsa-miR-34a target genes were concentrated in biological signaling pathways such as botulinum toxin B and G toxicities,cell adhesion and migration inhibition mediated by semaphorin 4D（Sema4D） and the synthesis and release of neurotransmitters. The target genes were reordered according to the protein interaction network. The target genes corresponding to the top 5 proteins were SYT1,VAMP2,MET,RRAS and CACNA1E. Conclusions The hsa-miR-34a is related to the occurrence and development of a variety of tumors. The analysis of its target genes and biological functions can provide a reference for subsequent clinical and basic research.

Key words: MicroRNA-34a, Bioinformatics analysis, Tumor, Target gene, Functional enrichment, Signaling pathway enrichment

CLC Number:

R446.7

WEN Shuzhan, FU Zile, CHEN Shuying. Expression and bioinformatics analysis of hsa-miR-34a in tumors[J]. Laboratory Medicine, 2022, 37(7): 657-663.

Figures/Tables 8

References 27

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疾病种类	表达情况	检测样本	作用	文献	发表年份
结肠癌	降低	细胞系	调节E2F信号通路,发挥细胞增殖抑制作用	TAZAWA等^[5]	2007年
		组织	p53通过miR-34a依赖性方式调节Fra-1蛋白表达,并最终调节细胞迁移和侵袭	WU等^[6]	2012年
绒毛膜癌	降低	细胞系	抑制Notch1和Jagged1基因的表达	PANG等^[7]	2010年
		细胞系	抑制DLL1基因的表达	PANG等^[8]	2013年
肾癌	降低	组织	调节YY1基因的表达,抑制细胞增殖	王明丽等^[9]	2012年
膀胱癌	降低	组织	拮抗Notch1蛋白并抑制膀胱癌细胞的迁移和侵袭	ZHANG等^[10]	2012年
		组织、细胞系、血液	靶向作用于CD44基因,发挥抑制转移和血管生成作用	YU等^[11]	2014年
骨肉瘤	降低	组织	体内外均可通过下调c-Met^①来抑制骨肉瘤细胞的迁移和侵袭	YAN等^[12]	2012年
		组织和细胞系	可以通过下调Eag1^②表达来抑制骨肉瘤的生长	WU等^[13]	2013年
乳腺癌	降低	细胞系	抑制细胞增殖和侵袭,诱导细胞凋亡	LI等^[14]	2013年
胃癌	降低	组织	通过PI3K^③/Akt^④通路靶向调控PDGFR^⑤和EMT^⑥,抑制胃癌发生	PENG等^[15]	2014年
肺腺癌	降低	组织	抑制p53负调节因子基因MDM4的表达	OKADA等^[16]	2014年
前列腺癌	降低	组织	通过抑制基因LEF1表达来抑制EMT,进而抑制前列腺肿瘤细胞的迁移和侵袭	LIANG等^[17]	2015年
宫颈癌	降低	组织	抑制LDHA^⑦,从而抑制肿瘤的Warburg效应,起到抑制肿瘤生长和迁移的作用	ZHANG等^[18]	2016年
非小细胞肺癌	降低	组织	下调PD-L1^⑧表达,从而抑制肿瘤的免疫逃逸	CORTEZ等^[19]	2015年
肝癌	降低	组织	调控HDAC1基因,抑制肝癌细胞增殖	SUN等^[20]	2017年

疾病种类	表达情况	检测样本	作用	文献	发表年份
结肠癌	降低	细胞系	调节E2F信号通路,发挥细胞增殖抑制作用	TAZAWA等^[5]	2007年
		组织	p53通过miR-34a依赖性方式调节Fra-1蛋白表达,并最终调节细胞迁移和侵袭	WU等^[6]	2012年
绒毛膜癌	降低	细胞系	抑制Notch1和Jagged1基因的表达	PANG等^[7]	2010年
		细胞系	抑制DLL1基因的表达	PANG等^[8]	2013年
肾癌	降低	组织	调节YY1基因的表达,抑制细胞增殖	王明丽等^[9]	2012年
膀胱癌	降低	组织	拮抗Notch1蛋白并抑制膀胱癌细胞的迁移和侵袭	ZHANG等^[10]	2012年
		组织、细胞系、血液	靶向作用于CD44基因,发挥抑制转移和血管生成作用	YU等^[11]	2014年
骨肉瘤	降低	组织	体内外均可通过下调c-Met^①来抑制骨肉瘤细胞的迁移和侵袭	YAN等^[12]	2012年
		组织和细胞系	可以通过下调Eag1^②表达来抑制骨肉瘤的生长	WU等^[13]	2013年
乳腺癌	降低	细胞系	抑制细胞增殖和侵袭,诱导细胞凋亡	LI等^[14]	2013年
胃癌	降低	组织	通过PI3K^③/Akt^④通路靶向调控PDGFR^⑤和EMT^⑥,抑制胃癌发生	PENG等^[15]	2014年
肺腺癌	降低	组织	抑制p53负调节因子基因MDM4的表达	OKADA等^[16]	2014年
前列腺癌	降低	组织	通过抑制基因LEF1表达来抑制EMT,进而抑制前列腺肿瘤细胞的迁移和侵袭	LIANG等^[17]	2015年
宫颈癌	降低	组织	抑制LDHA^⑦,从而抑制肿瘤的Warburg效应,起到抑制肿瘤生长和迁移的作用	ZHANG等^[18]	2016年
非小细胞肺癌	降低	组织	下调PD-L1^⑧表达,从而抑制肿瘤的免疫逃逸	CORTEZ等^[19]	2015年
肝癌	降低	组织	调控HDAC1基因,抑制肝癌细胞增殖	SUN等^[20]	2017年

序列号	物种	名称	保守序列	染色体定位
MI0000268	人	hsa-miR-34a	22-UGGCAGUGU-30	chr1：9151668-9151777 [-]^①
MI0002798	倭黑猩猩	ppa-miR-34a	22-UGGCAGUGU-30	chr1：9141308-9141417 [-]^①
MI0002801	猕猴	mml-miR-34a	22-UGGCAGUGU-30	chr1：8320927-8321036 [-]^①
MI0002799	婆罗洲猩猩	ppy-miR-34a	22-UGGCAGUGU-30	chr1：221288574-221288683 [+]^②
MI0000584	小鼠	mmu-miR-34a	20-UGGCAGUGU-28	chr4：150068454-150068555 [+]^②
MI0001251	原鸡	gga-miR-34a	21-UGGCAGUGU-29	chr21：3262992-3263100 [-]^①
MI0008101	家犬	cfa-miR-34a	1-UGGCAGUGU-9	chr5：62485832-62485897 [-]^①
MI0010019	文昌鱼	bfl-miR-34a	21-UGGCAGUGU-29

序列号	物种	名称	保守序列	染色体定位
MI0000268	人	hsa-miR-34a	22-UGGCAGUGU-30	chr1：9151668-9151777 [-]^①
MI0002798	倭黑猩猩	ppa-miR-34a	22-UGGCAGUGU-30	chr1：9141308-9141417 [-]^①
MI0002801	猕猴	mml-miR-34a	22-UGGCAGUGU-30	chr1：8320927-8321036 [-]^①
MI0002799	婆罗洲猩猩	ppy-miR-34a	22-UGGCAGUGU-30	chr1：221288574-221288683 [+]^②
MI0000584	小鼠	mmu-miR-34a	20-UGGCAGUGU-28	chr4：150068454-150068555 [+]^②
MI0001251	原鸡	gga-miR-34a	21-UGGCAGUGU-29	chr21：3262992-3263100 [-]^①
MI0008101	家犬	cfa-miR-34a	1-UGGCAGUGU-9	chr5：62485832-62485897 [-]^①
MI0010019	文昌鱼	bfl-miR-34a	21-UGGCAGUGU-29

GO序列	细胞组分名称	P值	基因数量	基因名称
60203	网格蛋白修饰的谷氨酸转运囊泡膜	2.98 ×10^-5	2	SYT1、VAMP2
60199	网格蛋白修饰的谷氨酸转运囊泡	2.98×10^-5	2	SYT1、VAMP2
70083	网格蛋白修饰的单胺运输囊泡膜	4.17×10^-5	2	SYT1、VAMP2
70081	网格蛋白修饰的单胺运输囊泡	4.17×10^-5	2	SYT1、VAMP2
61202	网格蛋白修饰的γ-氨基丁酸转运囊泡膜	8.92×10^-5	2	SYT1、VAMP2