CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression

Abstract

Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein. We had reported that CPEB3 is involved in hepatocellular carcinoma (HCC) progression. However, the underlying mechanisms of CPEB3 in HCC remain unclear. In this study, we firstly performed RNA immunoprecipitation to uncover the transcriptome-wide CPEB3-bound mRNAs (CPEB3 binder) in HCC. Bioinformatic analysis indicates that CPEB3 binders are closely related to cancer progression, especially HCC metastasis. Further studies confirmed that metadherin (MTDH) is a direct target of CPEB3. CPEB3 can suppress the translation of MTDH mRNA in vivo and in vitro. Besides, luciferase assay demonstrated that CPEB3 interacted with 3′-untranslated region of MTDH mRNA and inhibited its translation. Subsequently, CPEB3 inhibited the epithelial–mesenchymal transition and metastasis of HCC cells through post-transcriptional regulation of MTDH. In addition, cpeb3 knockout mice are more susceptible to carcinogen-induced hepatocarcinogenesis and subsequent lung metastasis. Our results also indicated that CPEB3 was a good prognosis marker, which is downregulated in HCC tissue. In conclusion, our results demonstrated that CPEB3 played an important role in HCC progression and targeting CPEB3-mediated mRNA translation might be a favorable therapeutic approach.

Mitochondrial Breast Cancer Resistant Protein Sustains the Proliferation and Survival of Drug-Resistant Breast Cancer Cells by Regulating Intracellular Reactive Oxygen Species

“…The detailed method for carryout quantitative real-time PCR (qRT-PCR) is previously described ( Zhang et al, 2020 ). Briefly, cells were lyzed using TRIzol reagent (Life Technologies, Carlsbad, CA, United States), and the RNA was isolated and reverse transcribed into cDNA.…”

Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance

“…It was documented that cytoplasmic polyadenylation element-binding protein 1 (CPEB1) binds to AEG-1 mRNA and increases its translation in glioblastoma cells [ 163 ]. On the other hand, in HCC cells, CPEB3, which functions as a tumor suppressor, binds to the 3′-untranslated region of AEG-1 mRNA and inhibits its translation [ 164 ]. Thus, AEG-1 overexpression in cancer occurs at all levels of gene regulation.…”

MiR-18a-5p Facilitates Progression of Hepatocellular Carcinoma by Targeting CPEB3

“…Present literature has confirmed that CPEB3 is vital in the progression of HCC. 29 For example, the study of Zhang et al 18 showed that CPEB3 can restrain EMT of HCC cells, and mice with CPEB3 knockout were more prone to develop liver cancer and lung metastasis. MiR-224 performs a tumor-promoting effect in HCC malignancies by targeting CPEB3.…”

“…Hansen et al 17 found that CPEB3 is down-regulated in cervical cancer. The study of Zhang et al 18 manifested that CPEB3 inhibits EMT of HCC cells, and mice with CPEB3 knockout are more prone to develop HCC and lung metastasis. These studies suggest that CPEB3 is vital in modulating the growth and development of various tumors, including HCC.…”