LAIR-1 suppresses cell growth of ovarian cancer cell via the PI3K-AKT-mTOR pathway
LAIR-1 suppresses cell growth of ovarian cancer cell via the PI3K-AKT-mTOR pathway
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LAIR-1通过PI3K-AKT-mTOR通路抑制卵巢癌细胞生长
DOI：
10.18632/aging.103589
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发表时间：
2020-08-31
期刊：
影响因子：
5.2
通讯作者：
Cao, Qizhi
中科院分区：
文献类型：
--
作者：
Liu, Yan;Ma, Li;Cao, Qizhi
最近，在包括卵巢癌在内的一些实体瘤中发现了LAIR-1的过度表达。LAIR-1在癌症进展中的作用需要进一步研究。在本研究中，我们鉴定了卵巢癌细胞HO 8910的LAIR-1 cDNA序列。使用SKOV 3细胞，我们证实了我们以前的研究发现，LAIR-1可以抑制体外细胞增殖和细胞迁移。LAIR-1过表达可诱导SKOV 3细胞凋亡。我们发现LAIR-1通过抑制PI 3 K-AKT-mTOR轴来抑制细胞生长。此外，LAIR-1的体内抗肿瘤活性和其机制也进行了鉴定。我们使用Co-IP分析和质谱来鉴定LAIR-1过表达SKOV 3细胞中潜在的LAIR-1结合蛋白。MS分析鉴定了167个可能相互作用的蛋白质。GO分析表明LAIR-1可能通过与一些真核翻译起始因子（eIF 4 E1 B、eIF 2S 3、eIF 3D、eIF 4G 2、eIF 5 B）和真核翻译延伸因子（eEF 1A 2和eEF 1B 2）相互作用参与mRNA加工。我们的研究结果表明，LAIR-1可能通过直接抑制PI 3 K-AKT-mTOR或在翻译水平调节蛋白质合成来抑制卵巢癌细胞的生长。我们的研究结果表明，基于LAIR-1的策略可以预防或抑制卵巢癌的进展。
Recently, over-expression of LAIR-1 has been found in some solid cancers, including ovarian cancer. The role of LAIR-1 in cancer progression needs further investigation. In this study, we identified the LAIR-1 cDNA sequence of the ovarian cancer cells HO8910. Using SKOV3 cells, we confirmed the finding from our previous study that LAIR-1 could suppress in vitro cell proliferation and cell migration. We also found LAIR-1 overexpression can induce apoptosis of SKOV3 cells. We revealed LAIR-1 suppressed cell growth by inhibiting the PI3K-AKT-mTOR axis. Moreover, the LAIR-1 antitumor activity and its mechanism were also identified in vivo. We used Co-IP assay and mass spectrometry to identify potential LAIR-1-binding proteins in LAIR-1 overexpressing SKOV3 cells. MS analysis identified 167 potentially interacting proteins. GO analyses indicated a possible involvement of LAIR-1 in mRNA processing through its interaction with some eukaryotic translation initiation factors (eIF4E1B, eIF2S3, eIF3D, eIF4G2, eIF5B) and eukaryotic translation elongation factors (eEF1A2 and eEF1B2). Our findings suggest that LAIR-1 may suppress the growth of ovarian cancer cells by serving as a modulator that suppresses PI3K-AKT-mTOR directly or regulating protein synthesis at the translational level. Our results indicate that a LAIR-1-based strategy may prevent or suppress the progression of ovarian cancer.