CNN2 Silencing Inhibits Colorectal Cancer Development Through Promoting Ubiquitination of EGR1.
Life science alliance(2023)
摘要
Colorectal cancer (CRC) is one of the most commonly diagnosed malignant tumors of the digestive tract. H2-calponin (CNN2), an actin cytoskeleton-binding protein, is an isoform of the calponin protein family whose role in CRC is still unknown. Research based on clinical samples showed the up-regulation of CNN2 in CRC and its association with tumor development, metastasis, and poor prognosis of patients. Both in vitro loss-of-function and gain-of-function experiments showed that CNN2 participates in CRC development through influencing malignant cell phenotypes. In vivo, xenografts formed by CNN2 knockdown cells also showed a slower growth rate and smaller final tumors. Furthermore, EGR1 was identified as a downstream of CNN2, forming a complex with CNN2 and YAP1 and playing an essential role in the CNN2-induced regulation of CRC development. Mechanistically, CNN2 knockdown down-regulated EGR1 expression through enhancing its ubiquitination, thus decreasing its protein stability in a YAP1-dependent manner. In summary, CNN2 plays an EGR1-dependent promotion role in the development and progression of CRC, which may be a promising therapeutic target for CRC treatment.
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