2. Academic Validation
  3. Docetaxel-resistant triple-negative breast cancer cell-derived exosomal lncRNA LINC00667 reduces the chemosensitivity of breast cancer cells to docetaxel via targeting miR-200b-3p/Bcl-2 axis

Docetaxel-resistant triple-negative breast cancer cell-derived exosomal lncRNA LINC00667 reduces the chemosensitivity of breast cancer cells to docetaxel via targeting miR-200b-3p/Bcl-2 axis

  • Eur J Histochem. 2022 Oct 25;66(4). doi: 10.4081/ejh.2022.3529.
Jindong Li 1,  Jie Kang 2,  Weiyan Liu 3,  Jiazhe Liu 4,  Gaofeng Pan 5,  Anwei Mao 6,  Qing Zhang 7,  Jingfeng Lu 8,  Junbin Ding 9,  Hongchang Li 10
Affiliations

Affiliations

  • 1 Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai. [email protected].
  • 2 Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai. [email protected].
  • 3 Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai. [email protected].
  • 4 Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai. [email protected].
  • 5 Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai. [email protected].
  • 6 Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai. [email protected].
  • 7 Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai. [email protected].
  • 8 Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai. [email protected].
  • 9 Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai. [email protected].
  • 10 Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai. [email protected].
PMID: 36281649 DOI: 10.4081/ejh.2022.3529
Abstract

Development of docetaxel (TXT) resistance is a major obstacle for triple-negative breast Cancer (TNBC) treatment. Additionally, chemoresistant cell-derived exosomes were able to change the chemo-response of chemosensitive recipient cells via transportation of lncRNAs. It has been shown that lncRNA LINC00667 level was significantly elevated in breast Cancer tissues. Therefore, we explored whether LINC00667 level is increased in TXT-resistant TNBC cell-derived exosomes. In addition, whether exosomal LINC00667 derived from TXT-resistant TNBC cell could affect TXT sensitivity in TXT-sensitive TNBC cells was investigated as well. In the present study, exosomes were isolated from the TXT-resistant TNBC cells and from TXT-sensitive TNBC cells. Next, the level of LINC00667 in the isolated exosomes was detected with RT-qPCR. We found that LINC00667 expression was obviously elevated in TXT-resistant TNBC cell-derived exosomes compared to that in TXT-sensitive TNBC cell-derived exosomes. In addition, LINC00667 could be transferred from TXT-resistant TNBC cells to TNBC cells via exosomes. Moreover, TXT-resistant TNBC cell secreted exosomal LINC00667 markedly reduced the sensitivity of TNBC cells to TXT via upregulation of Bcl-2. Meanwhile, downregulation of LINC00667 notably enhanced the sensitivity of TXT-resistant TNBC cells to TXT through downregulation of Bcl-2. Additionally, LINC00667 was considered to be a ceRNA to Sponge miR-200b-3p, thereby elevating Bcl-2 expression. Collectively, TXT-resistant TNBC cell-derived exosomal LINC00667 could decrease the chemosensitivity of TNBC cells to TXT via regulating miR-200b-3p/Bcl-2 axis. These findings suggested that LINC00667 might serve as a promising target for enhancing sensitivity of TNBC cells to TXT therapy.

Figures
Products