LINC00313 Facilitates Osteosarcoma Carcinogenesis and Metastasis Through Enhancing EZH2 MRNA Stability and EZH2-mediated Silence of PTEN Expression

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2022 Jun 25

PMID 35751755

Authors

Chun-Yang Xing

Yu-Zhu Zhang

Wei Hu

Li-Yuan Zhao

Affiliations

Soon will be listed here.

Abstract

Background: Osteosarcoma is one of the five leading causes of cancer death among all pediatric malignancies. Recent advances in non-coding RNAs suggested that many long noncoding RNAs (lncRNAs) are dysregulated in cancer tissues and play important roles in carcinogenesis. We aimed to further explore the mechanisms of Long Intergenic Non-Protein Coding RNA 313 (LINC00313)-promoted malignant phenotypes of osteosarcoma.

Methods: The mRNA expressions were determined by quantitative real-time PCR. Protein levels were detected using Western blotting or immunohistochemistry staining. Protein binding to genomic DNA and RNA were measured using chromatin and RNA immunoprecipitation assay, respectively. CCK-8 and EdU incorporation assay were adopted to detect cell proliferation. Transwell assay was employed to assess the capacity of cell migration and invasion. The roles of LINC00313 and its target genes in tumorigenesis and metastasis of osteosarcoma were evaluated using subcutaneous xenograft models and tail vein inoculation models.

Results: LINC00313 was elevated in osteosarcoma tissues compared with adjacent normal tissues. Higher LINC00313 was associated with advanced grades of osteosarcoma. LINC00313 promoted cell proliferation, migration, invasion in vitro and tumor growth as well as metastasis in vivo through inhibiting PTEN expression to promote AKT phosphorylation. Mechanistically, LINC00313 favored the interaction between FUS and EZH2, leading to the prolonged half-life of EZH2 mRNA, thereby in turn up-regulating EZH2 proteins and increasing EZH2-mediated epigenetic silence of PTEN.

Conclusion: LINC00313 exerted oncogene-like actions through increasing EZH2 mRNA stability, leading to PTEN deficiency in osteosarcoma.

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