A novel microRNA-182/Interleukin-8 regulatory axis controls osteolytic bone metastasis of lung cancer

被引:12
作者
Zhao, Ming-Na [1 ,2 ]
Zhang, Ling-Fei [3 ,4 ]
Sun, Zhen [4 ,5 ]
Qiao, Li-Hua [2 ]
Yang, Tao [5 ]
Ren, Yi-Zhe [2 ]
Zhang, Xian-Zhou [2 ]
Wu, Lei [2 ]
Qian, Wen-Li [2 ]
Guo, Qiao-Mei [2 ]
Xu, Wan-Xing [2 ]
Wang, Xue-Qing [2 ]
Wu, Fei [2 ]
Wang, Lin [2 ]
Gu, Yutong [6 ]
Liu, Mo-Fang [3 ,4 ,5 ]
Lou, Jia-Tao [2 ]
机构
[1] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Lab Med, Shanghai 200030, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Lab Med, Sch Med, Shanghai 200080, Peoples R China
[3] Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou 310024, Peoples R China
[4] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci,State Key Lab Mol Biol, Shanghai 200030, Peoples R China
[5] Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
[6] Fudan Univ, Zhongshan Hosp, Dept Orthopaed Surg, Shanghai 200030, Peoples R China
基金
中国国家自然科学基金; 上海市自然科学基金;
关键词
BREAST-CANCER; KAPPA-B; MIR-182; EXPRESSION; COLONIZATION; CELLS; INTERLEUKIN-8; INFLAMMATION; PATHWAY; PROTEIN;
D O I
10.1038/s41419-023-05819-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Bone metastasis is one of the main complications of lung cancer and most important factors that lead to poor life quality and low survival rate in lung cancer patients. However, the regulatory mechanisms underlying lung cancer bone metastasis are still poor understood. Here, we report that microRNA-182 (miR-182) plays a critical role in regulating osteoclastic metastasis of lung cancer cells. We found that miR-182 was significantly upregulated in both bone-metastatic human non-small cell lung cancer (NSCLC) cell line and tumor specimens. We further demonstrated that miR-182 markedly enhanced the ability of NSCLC cells for osteolytic bone metastasis in nude mice. Mechanistically, miR-182 promotes NSCLC cells to secrete Interleukin-8 (IL-8) and in turn facilitates osteoclastogenesis via activating STAT3 signaling in osteoclast progenitor cells. Importantly, systemically delivered IL-8 neutralizing antibody inhibits NSCLC bone metastasis in nude mice. Collectively, our findings identify the miR-182/IL-8/STAT3 axis as a key regulatory pathway in controlling lung cancer cell-induced osteolytic bone metastasis and suggest a promising therapeutic strategy that targets this regulatory axis to interrupt lung cancer bone metastasis.
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页数:13
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共 57 条
  • [1] A Combined PD-1/C5a Blockade Synergistically Protects against Lung Cancer Growth and Metastasis
    Ajona, Daniel
    Ortiz-Espinosa, Sergio
    Moreno, Haritz
    Lozano, Teresa
    Pajares, Maria J.
    Agorreta, Jackeline
    Bertolo, Cristina
    Lasarte, Juan J.
    Vicent, Silvestre
    Hoehlig, Kai
    Vater, Axel
    Lecanda, Fernando
    Montuenga, Luis M.
    Pio, Ruben
    [J]. CANCER DISCOVERY, 2017, 7 (07) : 694 - 703
  • [2] Deregulated miRNAs in osteoporosis: effects in bone metastasis
    Bellavia, Daniele
    Salamanna, F.
    Raimondi, L.
    De Luca, A.
    Carina, V.
    Costa, V.
    Alessandro, R.
    Fini, M.
    Giavaresi, G.
    [J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2019, 76 (19) : 3723 - 3744
  • [3] Bendre MS, 2002, CANCER RES, V62, P5571
  • [4] An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency
    Brady, Jennifer J.
    Chuang, Chen-Hua
    Greenside, Peyton G.
    Rogers, Zoe N.
    Murray, Christopher W.
    Caswell, Deborah R.
    Hartmann, Ursula
    Connolly, Andrew J.
    Sweet-Cordero, E. Alejandro
    Kundaje, Anshul
    Winslow, Monte M.
    [J]. CANCER CELL, 2016, 29 (05) : 697 - 710
  • [5] MicroRNAs in the control of metastatic bone disease
    Browne, Gillian
    Taipaleenmaeki, Hanna
    Stein, Gary S.
    Stein, Janet L.
    Lian, Jane B.
    [J]. TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2014, 25 (06) : 320 - 327
  • [6] microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11
    Cai, Wei-Luo
    Huang, Wen-Ding
    Li, Bo
    Chen, Tian-Rui
    Li, Zhen-Xi
    Zhao, Cheng-Long
    Li, Heng-Yu
    Wu, Yan-Mei
    Yan, Wang-Jun
    Xiao, Jian-Ru
    [J]. MOLECULAR CANCER, 2018, 17
  • [7] Chen HC, 2019, INT J CLIN EXP PATHO, V12, P4193
  • [8] Inferior outcome of bone metastasis in non-small-cell-lung-cancer patients treated with epidermal growth factor receptor inhibitors
    Chen, Yue-Yun
    Wang, Pei-Pei
    Yang-Fu
    Qing-Li
    Tian, Jiang-Fang
    Ting-Liu
    Lin, Zhen
    Ding, Zhen-Yu
    [J]. JOURNAL OF BONE ONCOLOGY, 2021, 29
  • [9] Molecular pathway for cancer metastasis to bone
    De, S
    Chen, JH
    Narizhneva, NV
    Heston, W
    Brainard, J
    Sage, EH
    Byzova, TV
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (40) : 39044 - 39050
  • [10] Tumor-Induced Osteoclast miRNA Changes as Regulators and Biomarkers of Osteolytic Bone Metastasis
    Ell, Brian
    Mercatali, Laura
    Ibrahim, Toni
    Campbell, Neil
    Schwarzenbach, Heidi
    Pantel, Klaus
    Amadori, Dino
    Kang, Yibin
    [J]. CANCER CELL, 2013, 24 (04) : 542 - 556