HES5 Activates Long Noncoding RNA UCA1 to Induce Colorectal Cancer Progression by Modulating miR-185/NOTCH3 Signaling

Mingming Wang; Qinlin Zheng; Zhengfei Zhao; Hong Deng; Qiang Zhang; Hui Yao

doi:10.1155/2021/7249818

HES5 Activates Long Noncoding RNA UCA1 to Induce Colorectal Cancer Progression by Modulating miR-185/NOTCH3 Signaling

Gastroenterol Res Pract. 2021 Oct 25:2021:7249818. doi: 10.1155/2021/7249818. eCollection 2021.

Authors

Mingming Wang¹, Qinlin Zheng², Zhengfei Zhao¹, Hong Deng¹, Qiang Zhang¹, Hui Yao¹

Affiliations

¹ Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, China.
² Department of Obstetrics and Gynecology, The Affiliated Hospital of Southwest Medical University, China.

Abstract

Colorectal cancer (CRC) is one of the most common diagnosed cancers around the world. The poor prognosis and high fatality caused by metastasis are still the challenges for clinical treatment. Therefore, it is promising to clarify the detailed molecular mechanism of CRC metastasis. Accumulating evidences indicate that long noncoding RNAs (lncRNAs) play important roles in cancer progression including CRC. In this study, the function of lncRNA UCA1 was investigated. UCA1 was confirmed to be highly expressed in colorectal cancer. Moreover, the UCA1 expression level was positively related to tumor stages. Silencing UCA1 showed inhibitory effect on cell proliferation and metastasis. Both UCA1 and NOTCH3 were validated as direct targets of miR-185. Silencing UCA1 repressed NOTCH3 expression through the miR-185 sponge. NOTCH3 was found to be highly expressed in CRC patients and positively related to UCA1 expression. Furthermore, HES5 was verified as a transcription factor of UCA1, which induced UCA1 expression. In conclusion, UCA1 is a direct target of HES5. UCA1 promotes CRC metastasis through regulating the miR-185/NOTCH3 axis.