Gao Chao, Li Li, Jin Xixin, Song Xinyu, Li Huiling, Xu Xiaoli, Dong Chao, Ma Binlin
State Key Laboratory of Pathogenes, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Breast and Thyroid Surgery, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, People's Republic of China.
State Key Laboratory of Pathogenes, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Gynecology and surgery, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, People's Republic of China.
Breast Cancer (Dove Med Press). 2022 Oct 10;14:311-322. doi: 10.2147/BCTT.S382566. eCollection 2022.
This study investigated the role and mechanism of insulin-like growth factor 2-IGF2BP2 in breast cancer.
IGF2BP2 is overexpressed in MDA-MB-231 human breast cancer cells. Thus, RNA sequencing was used to analyze the differentially expressed genes, Cell Counting Kit-8 was used to detect cell proliferation, and a Transwell assay was used to assess cell invasion. Following on from the RNA sequencing results, Interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), chemokine C-C motif ligand 20 (CCL20), chemokine C-C motif ligand 5 (CCL5), and chemokine C-X-C motif ligand 10 (CXCL10) regulated by IGF2BP2 were subjected to real-time reverse transcriptase-polymerase chain reaction verification.
After IGF2BP2 overexpression, 67 genes were up-regulated, and 87 genes were down-regulated. The gene with the most significant up-regulation was homeobox protein 1 (PROX1), and the gene with the most significant down-regulation was Acidic β-crystallin 4 (CRYBA4). The most enriched gene ontology (GO) terms of up-regulated differentially expressed genes are protein binding and cell membrane and of down-regulated differentially expressed genes they are ion binding, cytoplasm, and response to virus. Kyoto Encyclopedia of Genes and Genomes analysis showed that the up-regulated differential genes were mainly enriched in protein processing, the endoplasmic reticulum, and the regulation of actin cytoskeleton, while down-regulated differential genes were mainly enriched in rheumatoid arthritis, chemokine signaling pathways, toll-like receptor signaling pathways, tumor necrosis factor signaling pathways, cytokine-cytokine receptor interaction, and Notch signaling pathways. IGF2BP2 overexpression significantly promoted the proliferation and invasion of breast cancer cells ( < 0.01). Compared with the control group, the IGF2BP2 overexpression group had significantly increased expressions of IFIT2, CCL20, and CXCL10 ( < 0.05).
IGF2BP2 may promote the invasion and proliferation of human breast cancer cells by up-regulating breast cancer-related genes, such as IFIT2, CCL20, and CXCL10.
本研究调查胰岛素样生长因子2-IGF2BP2在乳腺癌中的作用及机制。
IGF2BP2在MDA-MB-231人乳腺癌细胞中过表达。因此,采用RNA测序分析差异表达基因,使用细胞计数试剂盒-8检测细胞增殖,并采用Transwell实验评估细胞侵袭。根据RNA测序结果,对受IGF2BP2调控的含四肽重复序列的干扰素诱导蛋白2(IFIT2)、趋化因子C-C基序配体20(CCL20)、趋化因子C-C基序配体5(CCL5)和趋化因子C-X-C基序配体10(CXCL10)进行实时逆转录-聚合酶链反应验证。
IGF2BP2过表达后,67个基因上调,87个基因下调。上调最显著的基因是同源框蛋白1(PROX1),下调最显著的基因是酸性β-晶状体蛋白4(CRYBA4)。上调的差异表达基因最富集的基因本体(GO)术语是蛋白质结合和细胞膜,下调的差异表达基因的是离子结合、细胞质和对病毒的反应。京都基因与基因组百科全书分析表明,上调的差异基因主要富集于蛋白质加工、内质网和肌动蛋白细胞骨架的调节,而下调的差异基因主要富集于类风湿性关节炎、趋化因子信号通路、Toll样受体信号通路、肿瘤坏死因子信号通路、细胞因子-细胞因子受体相互作用和Notch信号通路。IGF2BP2过表达显著促进乳腺癌细胞的增殖和侵袭(<0.01)。与对照组相比,IGF2BP2过表达组的IFIT2、CCL20和CXCL10表达显著增加(<0.05)。
IGF2BP2可能通过上调乳腺癌相关基因如IFIT2、CCL20和CXCL10来促进人乳腺癌细胞的侵袭和增殖。