The upregulation of the circular RNA (circ_0059961) increases the expression of secreted frizzled-related protein 2 (SFRP2) by targeting miR-629-5p, a new study published in Pathology – Research and Practice found. This blocks the proliferation, migration, and invasion of cholangiocarcinoma tumor cells.

“Our research indicated that circ_0059961 could be attached as a new biomarker for assessing [cholangiocarcinoma] prognosis and targeting treatment,” the researchers wrote.

It is thought that the pathophysiology of cholangiocarcinoma may be linked to the dysregulation of circular RNAs. Here, a team of researchers from China elucidated the role of circ_0059961 in cholangiocarcinoma.


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They found that the expression of circ_0059961 was decreased in cholangiocarcinoma tissues and cells. When circ_0059961 was overexpressed, tumor cell proliferation, migration, and invasion were reduced. Circ_0059961 overexpression also induced apoptosis.

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“Circ_0059961 was proven to be a target of miR-629-5p while miR-629-5p was confirmed to be a target of SFRP2,” the researchers wrote. “Circ_0059961 targeted miR-629-5p to modulate SFRP2 expression.”

In rescue experiments, the upregulating miR-629-5p reversed the tumor-suppressive effects of overexpressing circ_0059961. Moreover, overexpressing SFRP2 restored cell proliferation, migration, and invasion that miR-629-5p enrichment promotes. Finally, upregulating circ_0059961 reduced the growth of solid tumors in vivo.

“Through the miR-629–5p/SFRP2 axis, upregulated circ_0059961 could suppress [cholangiocarcinoma] cell proliferation, metastasis and carcinogenicity,” the researchers concluded.

Circular RNAs are single-stranded transcripts with closed-loop structures, which play critical biological roles. Circ_0059961 is a newly discovered circular RNA, the aberrant expression of which may be involved in carcinogenesis.

SFRP2 is known to play a role in regulating cell growth and differentiation, and miR-629-5p is a microRNA that has been shown to promote the growth and metastasis of many types of cancer.

Reference

Zhang X, Zhao Y, Wang W, et al. Upregulation of circ_0059961 suppresses cholangiocarcinoma development by modulating miR-629-5p/SFRP2 axis. Pathol Res Pract. Published online April 19, 2022. doi:10.1016/j.prp.2022.153901