Aberrant expression of the extracellular matrix component Biglycan regulated by Hedgehog signalling promotes colorectal cancer cell proliferation

Shaopeng Zeng; Feifei Zhou; Yiqing Wang; Zhenyu Zhai; Linlin Xu; Hailong Wang; Xinping Chen; Shiwen Luo; Minzhang Cheng

doi:10.3724/abbs.2021018

Aberrant expression of the extracellular matrix component Biglycan regulated by Hedgehog signalling promotes colorectal cancer cell proliferation

Acta Biochim Biophys Sin (Shanghai). 2022 Jan 25;54(2):243-251. doi: 10.3724/abbs.2021018.

Authors

Shaopeng Zeng^{1

2}, Feifei Zhou^{1

2

3}, Yiqing Wang^{1

2}, Zhenyu Zhai^{1

2}, Linlin Xu^{1

2}, Hailong Wang^{1

2}, Xinping Chen⁴, Shiwen Luo^{1

2}, Minzhang Cheng^{1

2}

Affiliations

¹ Center for Experimental Medicine, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
² Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang 330006, China.
³ School of Basic Medical Sciences, Nanchang University, Nanchang 330006, China.
⁴ Department of Obstetrics & Gynecology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.

Abstract

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 . 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.

Keywords: Hedgehog signalling; RNA-Seq; biglycan; colorectal cancer.

MeSH terms

Biglycan / genetics
Biglycan / metabolism
Cell Proliferation / genetics
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / metabolism
Extracellular Matrix / metabolism
Female
Hedgehog Proteins* / genetics
Humans
Pregnancy

Substances

Biglycan
Hedgehog Proteins

Grants and funding

This work was supported in part by the grants from the National Natural Science Foundation of China (No. 31900559 to M.C., No. 31671476 to S.L., No. 82060517 to L.X., No. 81860491 to Z.Z., and No. 82160507 to H.W.) and the Natural Science Foundation of Jiangxi Province (No. 20181BAB214009 to M.C., No. 20192BAB205061 to Z.Z., and No. 20202BABL206101 to X.C.).