2. Academic Validation
  3. Tumor-derived extracellular vesicles confer 5-fluorouracil resistance in esophageal cancer via long noncoding RNA AC116025.2 delivery

Tumor-derived extracellular vesicles confer 5-fluorouracil resistance in esophageal cancer via long noncoding RNA AC116025.2 delivery

  • Mol Carcinog. 2022 Oct 14. doi: 10.1002/mc.23469.
Shuyao Zhang 1,  Shaojie Liu 2,  Jingqing Ren 2,  Hanshuo Zhang 2,  Song Chen 3,  Yun Chen 1,  Shengqi Zhang 4 5,  Wang Chen 1,  Chengcheng Xu 1,  Shilong Zhong 6,  Sulin Liu 7,  Chaoxian Lin 8
Affiliations

Affiliations

  • 1 Department of Pharmacy, Guangzhou Red Cross Hospital (Guangzhou Red Cross Hospital of Jinan University), Jinan University, Guangzhou, China.
  • 2 Department of Gastrointestinal Surgery, Guangzhou Red Cross Hospital (Guangzhou Red Cross Hospital of Jinan University), Jinan University, Guangzhou, China.
  • 3 Department of Medical Imaging, Guangzhou Red Cross Hospital (Guangzhou Red Cross Hospital of Jinan University), Jinan University, Guangzhou, China.
  • 4 Dafeng Hospital of Chaoyang District in Shantou City, Shantou, China.
  • 5 Department of Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China.
  • 6 Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • 7 The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
  • 8 Shantou Chaonan Minsheng Hospital, Shantou, China.
PMID: 36239547 DOI: 10.1002/mc.23469
Abstract

5-Fluorouracil (5-FU) resistance is one of the main causes for treatment failure in esophageal Cancer (EC). Here, we intended to elucidate the mechanism of tumor-derived extracellular vesicles (TEVs)-encapsulated long noncoding RNAs (lncRNAs) AC116025.2 in 5-FU resistance in EC. EVs were isolated from the serum samples of EC patients and HEEC, TE-1, and TE-1/5-FU cells, followed by RT-qPCR detection of AC116025.2 expression in EVs. The relationship among AC116025.2, MicroRNA (miR)-4496, and SEMA5A was evaluated. Next, EC cells were cocultured with EVs, followed by lentivirus transduction and plasmid transfection for studying the role of TEVs-AC116025.2 in EC cells in relation to miR-4496 and SEMA5A. Tumor formation in nude mice was applied for in vivo confirmation. Elevated AC116025.2 expression was seen in the EVs from the serum of 5-FU insensitive patients and from 5-FU-resistant EC cells. Mechanistically, AC116025.2 bound to miR-4496 that inversely targeted SEMA5A in EC cells. EVs-oe-AC116025.2 augmented EC cell viability, colony formation, and 5-FU resistance, but diminished their Apoptosis through miR-4496-mediated SEMA5A. Furthermore, EVs-oe-AC116025.2 augmented tumor formation and 5-FU resistance of EC cells in vivo. Conclusively, our data offered evidence of the promoting mechanism of TEVs in the 5-FU resistance of EC by delivering AC116025.2.

Keywords

5-fluorouracil resistance; SEMA5A; esophageal cancer; long noncoding RNA AC116025.2; microRNA-4496; tumor cell-derived extracellular vesicles.

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