Journal Article

LncRNA TMPO-AS1 promotes esophageal squamous cell carcinoma progression by forming biomolecular condensates with FUS and p300 to regulate TMPO transcription

Chen, Dong-Liang, Luo, Kong-Jia, Liu, Ze-Xian, Xu, Rui-Hua, Zeng, Zhao-Lei, Luo, Xiao-Jing, He, Ming-Ming, Luo, Hui-Yan, Meng, Qi, Liu, Jia, Wu, Qi-Nian, Zheng, Jia-Bo, Chen, Yan-Xing

2022

Overview

Esophageal squamous cell carcinoma (ESCC) is one of the most life- and health-threatening malignant diseases worldwide, especially in China. Long noncoding RNAs (lncRNAs) have emerged as important regulators of tumorigenesis and tumor progression. However, the roles and mechanisms of lncRNAs in ESCC require further exploration. Here, in combination with a small interfering RNA (siRNA) library targeting specific lncRNAs, we performed MTS and Transwell assays to screen functional lncRNAs that were overexpressed in ESCC. TMPO-AS1 expression was significantly upregulated in ESCC tumor samples, with higher TMPO-AS1 expression positively correlated with shorter overall survival times. In vitro and in vivo functional experiments revealed that TMPO-AS1 promotes the proliferation and metastasis of ESCC cells. Mechanistically, TMPO-AS1 bound to fused in sarcoma (FUS) and recruited p300 to the TMPO promoter, forming biomolecular condensates in situ to activate TMPO transcription in cis by increasing the acetylation of histone H3 lysine 27 (H3K27ac). Targeting TMPO-AS1 led to impaired ESCC tumor growth in a patient-derived xenograft (PDX) model. We found that TMPO-AS1 is required for cell proliferation and metastasis in ESCC by promoting the expression of TMPO , and both TMPO-AS1 and TMPO might be potential biomarkers and therapeutic targets in ESCC. Esophageal cancer: Regulatory RNA increases a hormone that promotes cancer The role of a regulatory RNA in promoting esophageal squamous cell carcinoma (ESCC) has been clarified, revealing molecular details that might help in cancer diagnosis and treatment. Xiao-Jing Luo and colleagues at Sun Yat-sen University in China found that overproduction of an RNA molecule called thymopoietin-antisense RNA 1 (TMPO-AS1) in ESCC tissue samples from cancer patients was associated with shorter survival times. Overproduction of this RNA promoted proliferation and spread (metastasis) of the cancer cells. Research on details of the molecular mechanisms involved showed that the RNA ultimately activated the gene that codes for the protein hormone thymopoietin, which has previously been linked with various cancers. The authors suggest that TMPO-AS1 and thymopoietin could serve as diagnostic biomarkers of cancer and become targets for anti-cancer drugs.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,생화학분자생물학회
• Subject: 13/109 / 13/89 / 14/19 / 14/32 / 38/1 / 38/77 / 38/90 / 59/5 / 631/337/384/2568 / 631/67/1504/1477 / 631/67/395 / 64/60 / 82/29 / 82/51 / Acetylation / Antisense RNA / Antisense therapy / Antitumor agents / Biomarkers / Biomedical and Life Sciences / Biomedicine / Biomolecular Condensates / Cell Line, Tumor / Cell Proliferation / Condensates / Disease Progression / Drug development / Esophageal cancer / Esophageal Neoplasms - genetics / Esophageal Squamous Cell Carcinoma - genetics / Esophageal Squamous Cell Carcinoma - metabolism / Esophageal Squamous Cell Carcinoma - pathology / Esophagus / FUS protein / Gene Expression Regulation, Neoplastic / Histone H3 / Histones / Humans / Lysine / Medical Biochemistry / Metastases / Metastasis / MicroRNAs - genetics / Molecular Medicine / Molecular modelling / Non-coding RNA / Nuclear Proteins - metabolism / Patients / RNA, Long Noncoding - genetics / RNA, Long Noncoding - metabolism / RNA, Small Interfering / RNA-Binding Protein FUS / Sarcoma / siRNA / Squamous cell carcinoma / Stem Cells / Therapeutic targets / Thymopoietins - genetics / Thymopoietins - metabolism / Tumorigenesis / Xenografts / 생화학