LncRNA CASC11 Promotes Hepatocellular Carcinoma Progression via Upregulation of UBE2T in a m6A-Dependent Manner.

Fei Chen,Liang Wang,Meijun Li

doi:10.3389/fonc.2021.772671

Abstract

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies and the third leading cause of cancer-related deaths worldwide. Besides, it has been revealed that long non-coding RNA (LncRNA) cancer susceptibility candidate 11 (CASC11) is involved in cancer progression. However, the functional role and underlying mechanism of CASC11 in HCC remains largely unknown. In this context, here, it was found that CASC11 was upregulated in HCC tissues and associated with tumor grades, metastasis, and prognosis of HCC patients. Functionally, CASC11 facilitated HCC cell proliferation, migration, and invasion in vitro, and enhanced tumor growth and metastasis in vivo. Mechanistically, CASC11 associated with and stabilized Ubiquitin-conjugating enzyme E2T (UBE2T) mRNA. To be specific, it decreased UBE2T N6-methyladenosine (m6A) level via recruiting ALKBH5. Moreover, CASC11 inhibited the association between UBE2T mRNA and m6A reader protein YTHDF2. Taken together, our findings demonstrate the epigenetic mechanism of CASC11 in the regulation of UBE2T expression and possibly provide a novel therapeutic target for HCC treatment.

Highlights

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies and the third leading cause of cancer-related deaths worldwide [1]
The results showed that HCC tissues exhibited higher cancer susceptibility candidate 11 (CASC11) expression compared with normal liver tissues (Figure 1A)
It was known that the overexpression of wild-type CASC11 instead of its mutant suppressed the degradation of Ubiquitin-conjugating enzyme E2T (UBE2T) mRNA (Figure 4I), whereas silence of CASC11 shortened the half-life of UBE2T mRNA (Figure 4J). These findings reveal that CASC11 increases UBE2T expression through enhancing the stability of UBE2T mRNA, which depends on the association with UBE2T mRNA

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies and the third leading cause of cancer-related deaths worldwide [1]. It is urgent to understand the underlying mechanism of HCC pathogenesis and progression, and develop novel and effective therapeutic techniques for HCC patients. Long non-coding RNAs (lncRNAs) are classified as noncoding RNAs that are featured with more than 200 nucleotides in length, without or with limited coding potential. They have been found to act as important regulators in modulating gene expression via multiple mechanisms. The clinical significance, the functional role, and the underlying regulatory mechanism of CASC11 in HCC are still unclear to a great extent

Methods

Results

Conclusion