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BIRC5 调节炎症性肿瘤微环境诱导的阴茎癌在体内外的恶化。

BIRC5 regulates inflammatory tumor microenvironment-induced aggravation of penile cancer development in vitro and in vivo.

机构信息

Department of Urology, Yantai Affiliated Hospital of Binzhou Medical University, No. 717 Jinbu Street, Muping DistinctYantai, 264100, Shandong, China.

出版信息

BMC Cancer. 2022 Apr 23;22(1):448. doi: 10.1186/s12885-022-09500-9.

DOI:10.1186/s12885-022-09500-9
PMID:35461228
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9035256/
Abstract

BACKGROUND

Baculoviral IAP repeat containing 5 (BIRC5) is overexpressed and plays as a key regulator in the progression of various human carcinomas. The inflammatory tumor microenvironment (ITM) is closely associated with the development of cancers. However, the role of BIRC5 in penile cancer (PC) and the ITM-induced abnormal progression of PC is still obscure.

METHODS

In this study, serum and tissues of patients with PC were recruited to evaluate the expression profile of BIRC5. We used PC cell lines (Penl1 and Penl2) and constructed a PC xenograft mice model to explore the effects of the silencing of BIRC5 on proliferation, migration, invasion and tumor growth, as well as survival of mice. Besides, interferon (IFN)-γ was utilized to mimic the ITM of PC cells.

RESULTS

Our results showed that BIRC5 was dramatically upregulated in the serum and tissues of PC patients, as well as PC cell lines. Knockdown of BIRC5 inhibited the proliferation, migration and invasion of PC cells. Meanwhile, it suppressed PC xenograft tumor growth and improved mice survival. Moreover, IFN-γ significantly aggravated PC progression both in vivo and in vitro while the silencing of BIRC5 reversed these unfavorable effects.

CONCLUSIONS

Taken together, our data revealed that BIRC5 silencing inhibited aggravation of PC cell processes and tumor development induced by ITM. This suggested that BIRC5 may function as a diagnosis and therapy target of PC in the future.

摘要

背景

杆状病毒 IAP 重复包含 5（BIRC5）过表达，并在各种人类癌的进展中充当关键调节剂。炎症肿瘤微环境（ITM）与癌症的发展密切相关。然而，BIRC5 在阴茎癌（PC）中的作用以及 ITM 诱导的 PC 异常进展仍然不清楚。

方法

在这项研究中，招募了 PC 患者的血清和组织，以评估 BIRC5 的表达谱。我们使用了 PC 细胞系（Penl1 和 Penl2）并构建了 PC 异种移植小鼠模型，以探讨沉默 BIRC5 对增殖、迁移、侵袭和肿瘤生长以及小鼠生存的影响。此外，干扰素（IFN）-γ 被用来模拟 PC 细胞的 ITM。

结果

我们的结果表明，BIRC5 在 PC 患者的血清和组织以及 PC 细胞系中显著上调。BIRC5 的敲低抑制了 PC 细胞的增殖、迁移和侵袭。同时，它抑制了 PC 异种移植肿瘤的生长并提高了小鼠的生存率。此外，IFN-γ 显著加重了体内和体外的 PC 进展，而 BIRC5 的沉默逆转了这些不利影响。

结论

总之，我们的数据表明，BIRC5 的沉默抑制了 ITM 诱导的 PC 细胞过程和肿瘤发展的加重。这表明 BIRC5 将来可能成为 PC 的诊断和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b263/9035256/906a92169f86/12885_2022_9500_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b263/9035256/df13e75efd6a/12885_2022_9500_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b263/9035256/d4cbea7e6cdd/12885_2022_9500_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b263/9035256/8efc6fedbcef/12885_2022_9500_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b263/9035256/906a92169f86/12885_2022_9500_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b263/9035256/df13e75efd6a/12885_2022_9500_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b263/9035256/d4cbea7e6cdd/12885_2022_9500_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b263/9035256/8efc6fedbcef/12885_2022_9500_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b263/9035256/906a92169f86/12885_2022_9500_Fig4_HTML.jpg

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