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

Mingming Wang,Zhengfei Zhao,Hong Deng,Qinlin Zheng,Qiang Zhang,Hui Yao,Lukas Hawinkels

doi:10.1155/2021/7249818

Mingming Wang, Zhengfei Zhao + Show 5 more

Open Access

https://doi.org/10.1155/2021/7249818

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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.

Highlights

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers around the world [1]
Since the competitive endogenous RNA (ceRNA) network is important for long noncoding RNAs (lncRNAs) function and regulation, here, we investigated the potential gene which is possibly regulated by miR-185
One of the challenges in CRC clinical treatment is metastasis which results in poor prognosis and high recurrence rate

Summary

Introduction

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers around the world [1]. In year 2018, nearly 1.8 million new CRC cases were diagnosed and over 800,000 deaths occurred due to metastasis [2]. The treatments for CRC have been improved recently, the poor prognosis and high fatality are still the challenges because of metastasis. It is promising to clarify the detailed molecular mechanisms of CRC metastasis and provide potential therapeutic targets. Accumulating evidences indicate that long noncoding RNAs (lncRNAs) play important roles in cancer progression including CRC [3]. Our study will investigate the function of lncRNA in CRC metastasis

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