LRIG2 regulates cell proliferation, migration and apoptosis of osteosarcoma.
LRIG2 regulates cell proliferation, migration and apoptosis of osteosarcoma.
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LRIG2调控骨肉瘤细胞增殖、迁移和凋亡
DOI：
10.1186/s12885-022-10123-3
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发表时间：
2022-10-01
期刊：
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
--
作者：
骨肉瘤（Osteosarcoma，OS）是一种恶性骨肿瘤，侵袭性强，预后差.富含亮氨酸重复序列和免疫球蛋白样结构域2（Leucine-rich repeats and immunoglobulin-like domains 2，LRIG 2）与多种肿瘤的预后不良密切相关，但LRIG 2在骨肉瘤中的作用及其分子机制尚不清楚。方法采用qRT-PCR、免疫印迹（WB）和免疫组化（IHC）方法检测LRIG 2在人骨肉瘤组织和细胞中的mRNA和蛋白表达。采用细胞计数Kit-8（CCK-8）、克隆形成、transwell、原位末端标记（TUNEL）和WB法检测OS细胞的增殖、迁移和凋亡能力及其分子机制。结果LRIG 2在骨肉瘤组织和骨肉瘤细胞株中高表达，其表达水平与患者的Enneking分期显著相关;敲低LRIG 2表达可显著抑制骨肉瘤细胞的增殖、迁移和促进凋亡。沉默LRIG 2也抑制裸鼠皮下移植瘤的生长。进一步的机制研究表明，LRIG 2缺陷导致细胞凋亡相关蛋白Bax、caspase 9和caspase 3的表达增加，而抗凋亡蛋白BCL 2的表达减少。LRIG 2沉默导致AKT信号的磷酸化减少，波形蛋白和N-cadherin的表达减少。结论LRIG 2在骨肉瘤中起癌基因作用，可能成为治疗骨肉瘤的新靶点。
BackgroundOsteosarcoma (OS) is one of the malignant bone tumors with strong aggressiveness and poor prognosis. Leucine-rich repeats and immunoglobulin-like domains2 (LRIG2) is closely associated with the poor prognosis of a variety of tumors, but the role of LRIG2 in osteosarcoma and the underlying molecular mechanism remains unclear.ObjectiveThe aim of this study was to determine the function of LRIG2 in OS and the related molecular mechanism on cell proliferation, apoptosis and migration of OS.MethodsThe mRNA and protein expression of LRIG2 in OS tissues and cells was detected by qRT-PCR, western blot (WB) assay and immunohistochemistry (IHC). The cell counting Kit-8 (CCK-8), clone formation, transwell, TdT-mediated dUTP Nick-End Labeling (TUNEL) and WB assay were applied to determine the proliferation, migration and apoptosis abilities of OS cells and its molecular mechanisms. Spontaneous metastasis xenografts were established to confirm the role of LRIG2 in vivo.ResultsLRIG2 exhibited high expression in OS tissues and OS cell lines and the expression of which was significantly correlated with Enneking stage of patients, knockdown LRIG2 expression significantly inhibited OS cell proliferation, migration and enhanced apoptosis. Silencing LRIG2 also suppressed the growth of subcutaneous transplanted tumor in nude mice. Further, the mechanism investigation revealed that the protein level of cell proapoptotic proteins (Bax, caspase9 and caspase3) all increased attributed to LRIG2 deficiency, whereas expression of anti-apoptotic protein BCL2 decreased. LRIG2 silencing led to the decrease phosphorylation of AKT signaling, a decrease expression of vimentin and N-cadherin. Additionally, silencing LRIG2 significantly decreased the rate of tumor growth and tumor size.ConclusionsLRIG2 acts as an oncogene in osteosarcoma, and it might become a novel target in the treatment of human OS.
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影响因子：
5.2
作者：
Oh, Ju Yeon;Kim, Eun Ho;Kong, Chang-Bae
通讯作者：
Kong, Chang-Bae
影响因子：
6
作者：
Smrke A;Anderson PM;Gulia A;Gennatas S;Huang PH;Jones RL
通讯作者：
Jones RL
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影响因子：
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作者：
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通讯作者：
Hedman, H
影响因子：
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作者：
Villanova L;Careccia S;De Maria R;Fiori ME
通讯作者：
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