Exosome miR-3184-5p inhibits gastric cancer growth by targeting XBP1 to regulate the AKT, STAT3, and IRE1 signalling pathways

被引:8
作者
Lin, Shuangming [1 ]
Que, Yonggu [1 ]
Que, Changrong [1 ]
Li, Fudi [1 ]
Deng, Maoqing [2 ]
Xu, Dongbo [1 ]
机构
[1] Fujian Med Univ, Dept Gastrointestinal & Anal Surg, Longyan Hosp 1, 105 Jiuyi North Rd, Zhongcheng 364000, Longyan, Peoples R China
[2] Fujian Med Univ, Longyan Hosp 1, Dept Lab, 105 Jiuyi North Rd, Zhongcheng 364000, Longyan, Peoples R China
关键词
cell growth; exosome; gastric cancer; miR-3184-5p; XBP-1; ENDOPLASMIC-RETICULUM STRESS; BREAST-CANCER; ER STRESS; CELL-PROLIFERATION; ACTIVATION; EXPRESSION; RNA; PROGRESSION; RESISTANCE; APOPTOSIS;
D O I
10.1111/ajco.13663
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNAs can regulate the transcription of protein-coding genes associated with the development and progression of cancer. In this study, we explored the potential diagnostic function of exosome miR-3184-5p in gastric cancer. This exosome was isolated from the blood samples of 150 patients with gastric cancer and 60 healthy participants. The mean particle size and concentration of serum exosome in the patients with gastric cancer were 104.6 nm (93.97-115.84) and 6.21e+009 particles/ml (5.15e+009-7.12e+009), respectively. miR-3184-5p expression was substantially downregulated in the patients with gastric cancer compared with that in the healthy participants. The gastric cancer cell line HGC-27 was cultured and transfected with the mimic and an inhibitor to overexpress and inhibit miR-3184-5p expression. miR-3184-5p strongly suppressed cell proliferation, migration, and invasion but induced cell apoptosis. Luciferase reporter assay revealed that XBP1 was the target of miR-3184-5p. miR-3184-5p substantially downregulated the expression of CD44, cyclin D1, MMP2, p65, p-AKT, and p-STAT3 but upregulated that of GRP78, IRE1, p-JNK, and CHOP. Moreover, miR-3184-5p cleaved caspase-12 and inhibited BCL-2 expression. These results suggested that the downregulation of miR-3184-5p in patients with gastric cancer might regulate the AKT, STAT3, and IRE1 pathways to promote the vitality of gastric cancer cells.
引用
收藏
页码:E27 / E38
页数:12
相关论文
共 49 条
  • [1] [Anonymous], 2000, Science, DOI [DOI 10.1126/SCIENCE.287.5453.664, 10.1126/science.287.5453.664]
  • [2] Mechanism of inositol-requiring enzyme 1-alpha inhibition in endoplasmic reticulum stress and apoptosis in ovarian cancer cells
    Barez, Shekufe Rezghi
    Atar, Ahmad Movahedian
    Aghaei, Mahmoud
    [J]. JOURNAL OF CELL COMMUNICATION AND SIGNALING, 2020, 14 (04) : 403 - 415
  • [3] MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004)
    Bartel, David P.
    [J]. CELL, 2007, 131 (04) : 11 - 29
  • [4] Targeting the IRE1-XBP1 axis to overcome endocrine resistance in breast cancer: Opportunities and challenges
    Barua, David
    Gupta, Ananya
    Gupta, Sanjeev
    [J]. CANCER LETTERS, 2020, 486 : 29 - 37
  • [5] Involvement of Endoplasmic Reticulum Stress in Inflammatory Bowel Disease: A Different Implication for Colonic and Ileal Disease?
    Bogaert, Sara
    De Vos, Martine
    Olievier, Kim
    Peeters, Harald
    Elewaut, Dirk
    Lambrecht, Bart
    Pouliot, Philippe
    Laukens, Debby
    [J]. PLOS ONE, 2011, 6 (10):
  • [6] Bu XF, 2016, AM J CANCER RES, V6, P924
  • [7] Analysis of long non-coding RNA expression profiles in gastric cancer
    Cao, Wei-Jun
    Wu, Hai-Lu
    He, Bang-Shun
    Zhang, Yu-Shu
    Zhang, Zhen-Yu
    [J]. WORLD JOURNAL OF GASTROENTEROLOGY, 2013, 19 (23) : 3658 - 3664
  • [8] The biology and role of CD44 in cancer progression: therapeutic implications
    Chen, Chen
    Zhao, Shujie
    Karnad, Anand
    Freeman, James W.
    [J]. JOURNAL OF HEMATOLOGY & ONCOLOGY, 2018, 11
  • [9] IRE1α-XBP1 pathway promotes melanoma progression by regulating IL-6/STAT3 signaling
    Chen, Cheng
    Zhang, Xuejun
    [J]. JOURNAL OF TRANSLATIONAL MEDICINE, 2017, 15
  • [10] Identification of the potential molecular mechanism and driving mutations in the pathogenesis of familial intestinal gastric cancer by whole exome sequencing
    Chen, Haixiang
    Wang, Juan
    Zhuang, Yi
    Wu, Hao
    [J]. ONCOLOGY REPORTS, 2018, 40 (04) : 2316 - 2324