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Circ-0075305 hinders gastric cancer stem cells by indirectly disrupting TCF4-ß-catenin complex and downregulation of SOX9.
Chen, Qi-Yue; Xu, Kai-Xiang; Huang, Xiao-Bo; Fan, Deng-Hui; Chen, Yu-Jing; Li, Yi-Fan; Huang, Qiang; Liu, Zhi-Yu; Zheng, Hua-Long; Huang, Ze-Ning; Lin, Ze-Hong; Wang, Yu-Xiang; Yang, Jun-Jie; Zhong, Qing; Huang, Chang-Ming.
Affiliation
  • Chen QY; Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Xu KX; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Huang XB; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
  • Fan DH; Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Chen YJ; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Li YF; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
  • Huang Q; Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Liu ZY; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Zheng HL; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
  • Huang ZN; Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Lin ZH; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Wang YX; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
  • Yang JJ; Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Zhong Q; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Huang CM; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
Commun Biol ; 7(1): 545, 2024 May 07.
Article in En | MEDLINE | ID: mdl-38714724
ABSTRACT
CircRNAs are covalently closed, single-stranded RNA that form continuous loops and play a crucial role in the initiation and progression of tumors. Cancer stem cells (CSCs) are indispensable for cancer development; however, the regulation of cancer stem cell-like properties in gastric cancer (GC) and its specific mechanism remain poorly understood. We elucidate the specific role of Circ-0075305 in GC stem cell properties. Circ-0075305 associated with chemotherapy resistance was identified by sequencing GC cells. Subsequent confirmation in both GC tissues and cell lines revealed that patients with high expression of Circ-0075305 had significantly better overall survival (OS) rates than those with low expression, particularly when treated with postoperative adjuvant chemotherapy for GC. In vitro and in vivo experiments confirmed that overexpression of Circ-0075305 can effectively reduce stem cell-like properties and enhance the sensitivity of GC cells to Oxaliplatin compared with the control group. Circ-0075305 promotes RPRD1A expression by acting as a sponge for corresponding miRNAs. The addition of LF3 (a ß-catenin/TCF4 interaction antagonist) confirmed that RPRD1A inhibited the formation of the TCF4-ß-catenin transcription complex through competitive to ß-catenin and suppressed the transcriptional activity of stem cell markers such as SOX9 via the Wnt/ß-catenin signaling pathway. This leads to the downregulation of stem cell-like property-related markers in GC. This study revealed the underlying mechanisms that regulate Circ-0075305 in GCSCs and suggests that its role in reducing ß-catenin signaling may serve as a potential therapeutic candidate.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stomach Neoplasms / Neoplastic Stem Cells / Down-Regulation / Gene Expression Regulation, Neoplastic / Beta Catenin / SOX9 Transcription Factor / Transcription Factor 4 / RNA, Circular Limits: Animals / Female / Humans / Male / Middle aged Language: En Journal: Commun Biol Year: 2024 Document type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stomach Neoplasms / Neoplastic Stem Cells / Down-Regulation / Gene Expression Regulation, Neoplastic / Beta Catenin / SOX9 Transcription Factor / Transcription Factor 4 / RNA, Circular Limits: Animals / Female / Humans / Male / Middle aged Language: En Journal: Commun Biol Year: 2024 Document type: Article Affiliation country: China