Aberrant expression of the extracellular matrix component Biglycan regulated by Hedgehog signalling promotes colorectal cancer cell proliferation.
Aberrant expression of the extracellular matrix component Biglycan regulated by Hedgehog signalling promotes colorectal cancer cell proliferation.
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受 Hedgehog 信号调节的细胞外基质成分 Biglycan 的异常表达可促进结直肠癌细胞增殖。
DOI：
10.3724/abbs.2021018
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发表时间：
2022-01-25
影响因子：
3.7
通讯作者：
Cheng, Minzhang
中科院分区：
文献类型：
--
作者：
Zeng, Shaopeng;Zhou, Feifei;Wang, Yiqing;Zhai, Zhenyu;Xu, Linlin;Wang, Hailong;Chen, Xinping;Luo, Shiwen;Cheng, Minzhang
Hedgehog（Hh）信号在调节胚胎发育中起着重要作用，并有助于多种癌症的肿瘤发生、生长和进展。Hh信号参与肿瘤生长的详细机制值得深入研究，尽管已经确定了几个下游靶基因。在本文中，通过RNA-Seq分析在多种类型的肿瘤细胞中鉴定了一组Hh信号传导的新靶标。在这些目标中，细胞外基质组分双糖链蛋白聚糖（BGN）的表达调控和致癌功能进行了研究。进一步的研究证实，Hh信号通过转录因子Gli 2激活BGN的表达，Gli 2直接结合到BGN的启动子区。功能测定显示BGN促进结直肠癌（CRC）细胞中的肿瘤细胞生长和增殖，并且异种移植测定证实BGN也促进体内肿瘤生长。此外，对临床结直肠癌样本的分析显示，与癌旁组织相比，BGN的蛋白和mRNA水平在结直肠癌组织中均升高，并且BGN的高表达与结直肠癌患者的较差预后相关，进一步证实了BGN在结直肠癌中的功能。总之，异常激活的Hh信号增加BGN的表达，可能调节细胞外基质，从而促进CRC中的肿瘤生长。
Hedgehog (Hh) signalling plays essential roles in regulating embryonic development and contributes to tumour initiation, growth and progression in multiple cancers. The detailed mechanism by which Hh signalling participates in tumour growth warrants thorough study, although several downstream target genes have been identified. Herein, a set of novel targets of Hh signalling was identified in multiple types of tumour cells via RNA-Seq analysis. Among these targets, the expression regulation and oncogenic function of the extracellular matrix component biglycan (BGN) were investigated. Further investigation verified that Hh signalling activates the expression of BGN via the transcription factor Gli2, which directly binds to the promoter region of BGN. Functional assays revealed that BGN facilitates tumour cell growth and proliferation in colorectal cancer (CRC) cells, and xenograft assays confirmed that BGN also promotes tumour growth in vivo. Moreover, analysis of clinical CRC samples showed that both the protein and mRNA levels of BGN are increased in CRC tissues compared to those in adjacent tissues, and higher expression of BGN is correlated with poorer prognosis of CRC patients, further confirming the function of BGN in CRC. Taken together, aberrantly activated Hh signalling increases the expression of BGN, possibly regulates the extracellular matrix, and thereby promotes tumour growth in CRC.
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