Interleukin-31 Receptor α Is Required for Basal-Like Breast Cancer Progression
Interleukin-31 Receptor α Is Required for Basal-Like Breast Cancer Progression
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Interleukin-31 受体 α 是基底样乳腺癌进展所必需的
DOI：
10.3389/fonc.2020.00816
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发表时间：
2020-05-27
影响因子：
4.7
通讯作者：
Shi, Jian
中科院分区：
文献类型：
--
作者：
He, Yanling;Zhang, Xinyuan;Shi, Jian
目的：白细胞介素 - 31受体α（IL31RA）通常介导白细胞介素 - 31诱导的炎症和过敏性疾病。然而，白细胞介素 - 31/白细胞介素31受体A信号在基底样乳腺癌（BLBC）进展中的功能作用仍完全不清楚。
方法：采用肿瘤球形成、Transwell和伤口愈合实验来检测基底样乳腺癌的进展。我们将肿瘤细胞接种到裸鼠的乳腺脂肪垫和尾静脉中，以检测基底样乳腺癌细胞的生长和转移。采用荧光素酶和染色质免疫沉淀（ChIP）实验来检测转录调控。进行蛋白质印迹和实时定量聚合酶链反应（PCR）实验以及生物信息学分析来观察白细胞介素31受体A的表达。
结果：我们发现沉默白细胞介素31受体A可抑制基底样乳腺癌细胞在体外的癌干细胞样特性、迁移和侵袭，以及在体内的肿瘤生长和转移。敲低白细胞介素31受体A可改善白细胞介素 - 31介导的促癌功能。在管腔型乳腺癌细胞中过表达白细胞介素31受体A可增强癌干细胞样特性和细胞运动性。我们的数据进一步确定白细胞介素31受体A是Twist/BRD4转录复合物的靶基因。
结论：总体而言，这些数据表明白细胞介素31受体A促进基底样乳腺癌的进展和转移，这提示靶向白细胞介素 - 31/白细胞介素31受体A轴可能有利于基底样乳腺癌的治疗。
Purpose: Interleukin-31 receptor alpha (IL31RA) usually mediates IL-31 induced inflammation and allergic diseases. However, the functional roles of IL-31/IL31RA signaling in basal-like breast cancer (BLBC) progression remain totally unclear.Methods: Tumorsphere formation, transwell, and wound healing assays were used to measure the BLBC progression. We implanted tumor cells in mammary fat pad and tail vein of nude mice to detect the growth and metastasis of BLBC cells. Luciferase and ChIP assays were employed to measure the transcriptional regulation. Western blot and real-time PCR assays as well as bio-informatics analyses were conducted to observe the expression of IL31RA.Results: We found that silencing of IL31RA suppresses the cancer stem cell-like properties, migration and invasion of BLBC cells in vitro as well as tumor growth and metastasis in vivo. Knockdown of IL31RA ameliorates IL-31-mediated pro-oncogenic functions. Overexpression of IL31RA in luminal breast cancer cells enhances the cancer stem cell-like properties and cell motility. Our data further identified IL31RA as a target gene of Twist/BRD4 transcription complex.Conclusion: Overall, these data indicate that IL31RA promotes basal-like breast cancer progression and metastasis, suggesting that targeting of IL-31/IL31RA axis might be beneficial to treatment of BLBC.