2. Academic Validation
  3. G3BP2 regulated by the lncRNA LINC01554 facilitates esophageal squamous cell carcinoma metastasis through stabilizing HDGF transcript

G3BP2 regulated by the lncRNA LINC01554 facilitates esophageal squamous cell carcinoma metastasis through stabilizing HDGF transcript

  • Oncogene. 2022 Jan;41(4):515-526. doi: 10.1038/s41388-021-02073-0.
Yinli Zheng # 1 2,  Jinjun Wu # 3,  Ru Deng # 1 2,  Censhan Lin # 1 2,  Yuhua Huang 1 2,  Xia Yang 1 2,  Chunhua Wang 1 2,  Mingming Yang 1 2,  Yangfan He 1 2,  Jiabin Lu 1 2,  Xiaodong Su 1 4,  Qian Yan 5,  Yinghui Zhu 1,  Xinyuan Guan 1 6 7,  Yan Li 8,  Jingping Yun 9 10
Affiliations

Affiliations

  • 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P. R. China.
  • 2 Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China.
  • 3 Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China.
  • 4 Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China.
  • 5 Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510000, PR China.
  • 6 Department of Clinical Oncology, State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, 852, PR China.
  • 7 Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 518053, PR China.
  • 8 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P. R. China. [email protected].
  • 9 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P. R. China. [email protected].
  • 10 Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China. [email protected].
  • # Contributed equally.
PMID: 34782720 DOI: 10.1038/s41388-021-02073-0
Abstract

Metastasis is the leading cause of death of patients with esophageal squamous cell carcinoma (ESCC). Although an increasing number of studies have demonstrated the involvement of G3BP2 in several human cancers, how G3BP2 interacts with long noncoding RNAs and regulates mRNA transcripts in mediating ESCC metastasis remains unclear. In this study, we uncovered that G3BP2 was upregulated in ESCC. Further analysis revealed that upregulation of G3BP2 was significantly correlated with lymph node metastasis, depth of tumor invasion and unfavorable outcomes in ESCC patients. Both in vitro and in vivo functional assays demonstrated that G3BP2 dramatically enhanced ESCC cell migration and invasion. Mechanistically, LINC01554 maintained the high G3BP2 expression in ESCC by protecting G3BP2 from degradation through ubiquitination and the interaction domains within LINC01554 and G3BP2 were identified. In addition, RNA-seq revealed that HDGF was regulated by G3BP2. G3BP2 bound to HDGF mRNA transcript to stabilize its expression. Ectopic expression of HDGF effectively abolished the G3BP2 depletion-mediated inhibitory effect on tumor cell migration. Intriguingly, introduction of compound C108 which can inhibit G3BP2 remarkedly suppressed ESCC cell metastasis in vitro and in vivo. Collectively, this study describes a newly discovered regulatory axis, LINC01554/G3BP2/HDGF, that facilitates ESCC metastasis and will provide novel therapeutic strategies for ESCC.

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