北京生物醫(yī)學(xué)工程

蟻群優(yōu)化算法構(gòu)建乳腺癌中miRNA調(diào)控的關(guān)鍵基因互作網(wǎng)絡(luò)

Construction of key gene interaction network of miRNA regulation in breast cancer by ant colony optimization

作者：張?zhí)N顯王雅梅周萍

單位：首都醫(yī)科大學(xué)生物醫(yī)學(xué)工程學(xué)院(北京 100069) 首都醫(yī)科大學(xué)基礎(chǔ)醫(yī)學(xué)院(北京 100069)

關(guān)鍵詞：生物信息學(xué)；基因互作網(wǎng)絡(luò)；富集分析；蟻群算法；乳腺癌

分類號(hào)：R318

出版年·卷·期（頁(yè)碼）：2019·38·4（369-376）

摘要：

目的篩選ER陽(yáng)性乳腺癌中受miRNA調(diào)控的關(guān)鍵基因，以此構(gòu)建乳腺癌中miRNA-mRNA互作網(wǎng)絡(luò)，進(jìn)而了解ER陽(yáng)性乳腺癌的調(diào)控機(jī)制，為篩選ER陽(yáng)性乳腺癌診斷預(yù)后的生物標(biāo)志物和治療靶點(diǎn)打下基礎(chǔ)。方法利用MCF-7細(xì)胞系的AGO-IP（HITS-CLIP Protocol for Argonaute）高通測(cè)序?qū)嶒?yàn)數(shù)據(jù)，發(fā)現(xiàn)miRNA對(duì)mRNA的真實(shí)調(diào)控關(guān)系，并以此構(gòu)建基于miRNAs誘導(dǎo)的沉默復(fù)合體（RISCs）miRNA-mRNA調(diào)控模組。根據(jù)調(diào)控模組利用蟻群優(yōu)化算法在基因互作網(wǎng)絡(luò)中篩選關(guān)鍵基因，構(gòu)建ER陽(yáng)性乳腺癌中miRNA調(diào)控下的關(guān)鍵基因互作網(wǎng)絡(luò)，并對(duì)關(guān)鍵基因進(jìn)行功能分析。結(jié)果本研究篩選出106個(gè)關(guān)鍵基因，244個(gè)調(diào)控關(guān)鍵基因的miRNA。根據(jù)乳腺癌中miRNA調(diào)控的關(guān)鍵基因互作網(wǎng)絡(luò)識(shí)別出了YWHAG、EP300、CHEK1、SMAD2、SMAD1、SYK、FGFR1、PIK3R2、IRS1、TGFBR2、CHUK和CSDE1等12個(gè)hub基因；并發(fā)現(xiàn)了hsa-miR-940、hsa-miR-545-3p、hsa-miR-3065-5p、hsa-miR-15a-5p、hsa-miR-181b-5p、hsa-miR-16-5p、hsa-miR-765、hsa-miR-4723-5p、hsa-miR-454-3p、hsa-miR-374a-5p、hsa-miR-34a-5p、hsa-miR-30e-5p、hsa-miR-19a-3p、hsa-miR-15b-5p、hsa-miR-149-5p和hsa-miR-128-3p等16個(gè)hub miRNA。這些基因主要對(duì)腫瘤細(xì)胞的增殖、侵襲、化療抗性、放療抗性和耐藥性起重要作用。結(jié)論本研究篩選出關(guān)鍵基因及調(diào)控關(guān)鍵基因的miRNA對(duì)ER陽(yáng)性乳腺癌的耐藥性、化療抗性、放療抗性及腫瘤細(xì)胞的增殖、侵襲起到了重要調(diào)控作用，對(duì)ER陽(yáng)性乳腺癌臨床治療及預(yù)后起到重要參考作用。

Objective To screen the key genes regulated by miRNA in ER+ breast cancer, and construct the miRNA-mRNA interaction network in breast cancer, so as to understand the regulatory mechanism of ER+ breast cancer, and lay the foundation for screening the biomarkers and treatment targets of ER+ breast cancer for diagnosis and prognosis. Methods By using the high-pass sequencing data of AGO-IP (HITS-CLIP Protocol for Argonaute) of MCF-7 cell line, we found the real relationship between miRNA and mRNA, and constructed a miRNA-mRNA regulatory module based on microRNAs-induced silencing complex (RISCs). According to the regulation module, ant colony optimization algorithm was used to screen key genes in gene interaction network, and constructed the key gene interaction network under the regulation of miRNA in ER+ breast cancer, and analyzed the function of key genes. Results In this study, 106 key genes and 244 microRNAs regulating key genes were screened. Twelve hub genes, including YWHAG, EP300, CHEK1, SMAD2, SMAD1, SYK, FGFR1, PIK3R2, IRS1, TGFBR2, CHUK, CSDEE1, and 16 hub miRNAs, including hsa-miR-940, hsa-miR-545-3p, hsa-miR-3065-5p, hsa-miR-15a-5p, hsa-miR-181b-5p, hsa-miR-16-5p, hsa-miR-765, hsa-miR-4723-5p, hsa-miR-454-3p, hsa-miR-374a-5p, hsa-miR-34a-5p, hsa-miR-30e-5p, hsa-miR-19a-3p, hsa-miR-15b-5p, sa-miR-149-5p, hsa-miR-128-3p, were identified according to the key gene interaction network regulated by miRNA in breast cancer. These genes played an important role in the proliferation, invasion, chemotherapy resistance, radiotherapy resistance and drug resistance of cancer cells. Conclusions In this study, we screened out the key genes and the miRNA that regulated the key genes, which played an important role in the regulation of ER+ breast cancer resistance, chemotherapy resistance, radiotherapy resistance, proliferation and invasion of cancer cells. It also played an important reference role in the clinical treatment and prognosis of ER+ breast cancer.

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