miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas

被引:64
|
作者
Lin, Shih-Shen [1 ,2 ]
Peng, Chih-Yu [1 ,2 ]
Liao, Yi-Wen [1 ]
Chou, Ming-Yung [1 ,2 ,3 ]
Hsieh, Pei-Ling [4 ]
Yu, Cheng-Chia [1 ,2 ,3 ]
机构
[1] Chung Shan Med Univ, Sch Dent, Taichung 40201, Taiwan
[2] Chung Shan Med Univ Hosp, Dept Dent, Taichung 40201, Taiwan
[3] Chung Shan Med Univ, Inst Oral Sci, Taichung 40201, Taiwan
[4] China Med Univ, Sch Med, Dept Anat, Taichung 40402, Taiwan
来源
CANCERS | 2018年 / 10卷 / 08期
关键词
oral squamous cell carcinomas; miR-1246; cancer stemness; chemoresistance; CCNG2; SQUAMOUS-CELL CARCINOMA; CYCLIN G2; MESENCHYMAL TRANSITION; MICRORNA EXPRESSION; PANCREATIC-CANCER; TUMOR-GROWTH; LUNG-CANCER; HEAD; PROMOTES; MARKER;
D O I
10.3390/cancers10080272
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MiRNAs have been recognized as crucial components in carcinogenesis, but whether miR-1246 affects the cancer sternness and drug resistance in oral squamous cell carcinoma (OSCC) has not been fully understood and its downstream targets still need to be unraveled. In the present work, we employed miRNAs RT-PCR analysis to evaluate the expression of miR-1246 in tumor tissues and oral cancer stem cells (OCSC). Stemness phenotypes, including self-renewal, migration, invasion, colony formation capacities, and in vivo oncogenicity of oral cancer cells following transfected with miR-1246 inhibitors or mimics were examined. Our results suggested that the expression level of miR-1246 was significantly upregulated in the tumor tissues and OCSC. Kaplan-Meier survival analysis of OSCC patients with high levels of miR-1246 had the worst survival rate compared to their low-expression counterparts. Inhibition of miR-1246 in OCSC significantly reduced the stemness hallmarks, while overexpression of miR-1246 enhanced these characteristics. Moreover, we showed that downregulation of miR-1246 decreased chemoresistance. In addition, we verified that miR-1246-inhibited CCNG2 contributed to the cancer stemness of OSCC. These results demonstrated the significance of miR-1246 in the regulation of OSCC stemness. Targeting miR-1246-CCNG2 axis may be beneficial to suppress cancer relapse and metastasis in OSCC patients.
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页数:14
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共 40 条
  • [1] Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer
    Li, Xiu Juan
    Ren, Zhao Jun
    Tang, Jin Hai
    Yu, Qiao
    [J]. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2017, 44 (05) : 1741 - 1748
  • [2] Identification of the crucial microRNA, miR-1246 related to the chemoresistance and stemness in pancreatic cancer for new targeting therapy
    Hasegawa, Shinichiro
    Hideshi, Ishii
    Eguchi, Hidetoshi
    Kobayashi, Shogo
    Wada, Hiroshi
    Hama, Naoki
    Tomimaru, Yoshito
    Koichi, Kawamoto
    Konno, Masamitsu
    Ogawa, Hisataka
    Nishikawa, Shimpei
    Kano, Yoshihiro
    Kano, Yoshihiro
    Fukusumi, Takahito
    Hamabe, Atsushi
    Nishimura, Takenori
    Hinohara, Kunihiko
    Satoh, Taroh
    Gotoh, Noriko
    Nagano, Hiroaki
    Doki, Yuichiro
    Mori, Masaki
    [J]. CANCER RESEARCH, 2014, 74 (19)
  • [3] MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer
    Hasegawa, S.
    Eguchi, H.
    Nagano, H.
    Konno, M.
    Tomimaru, Y.
    Wada, H.
    Hama, N.
    Kawamoto, K.
    Kobayashi, S.
    Nishida, N.
    Koseki, J.
    Nishimura, T.
    Gotoh, N.
    Ohno, S.
    Yabuta, N.
    Nojima, H.
    Mori, M.
    Doki, Y.
    Ishii, H.
    [J]. BRITISH JOURNAL OF CANCER, 2014, 111 (08) : 1572 - 1580
  • [4] MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer
    S Hasegawa
    H Eguchi
    H Nagano
    M Konno
    Y Tomimaru
    H Wada
    N Hama
    K Kawamoto
    S Kobayashi
    N Nishida
    J Koseki
    T Nishimura
    N Gotoh
    S Ohno
    N Yabuta
    H Nojima
    M Mori
    Y Doki
    H Ishii
    [J]. British Journal of Cancer, 2014, 111 : 1572 - 1580
  • [5] MiR-1290 targets CCNG2 to promote the metastasis of oral squamous cell carcinoma
    Qin, W-J
    Wang, W-P
    Wang, X-B
    Zhang, X-T
    Du, J-D
    [J]. EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES, 2019, 23 (23) : 10332 - 10342
  • [6] 5′-Isoforms of miR-1246 Have Distinct Targets and Stronger Functional Impact Compared with Canonical miR-1246 in Colorectal Cancer Cells In Vitro
    Lukosevicius, Rokas
    Alzbutas, Gediminas
    Varkalaite, Greta
    Salteniene, Violeta
    Tilinde, Deimante
    Juzenas, Simonas
    Kulokiene, Ugne
    Janciauskas, Dainius
    Poskiene, Lina
    Adamonis, Kestutis
    Kiudelis, Gediminas
    Kupcinskas, Juozas
    Skieceviciene, Jurgita
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2024, 25 (05)
  • [7] miR-155-5p and miR-1246 as promising biomarkers in oral squamous cell carcinomas
    Ramamoorthy, Maheswari
    Guru, Sameer A.
    Koner, Bhidhan C.
    Kumar, Priya
    Urs, Aadithya B.
    [J]. ANNALS OF ONCOLOGY, 2022, 33 : S498 - S499
  • [8] Tumor heterogeneity: Extracellular vesicles mediated transport of melanoma cell-derived miR-1246 between subpopulations of melanoma cells enhances the invasive capacity by targeting CCNG2
    Kingreen, T.
    Kewitz-Hempel, S.
    Rhode, C.
    Hause, G.
    Sunderkoetter, C.
    Gerloff, D.
    [J]. EXPERIMENTAL DERMATOLOGY, 2024, 33 (03)
  • [9] MicroRNA-1246 promotes growth and metastasis of colorectal cancer cells involving CCNG2 reduction
    Wang, Sai
    Zeng, Ya
    Zhou, Ju-Mei
    Nie, Shao-Lin
    Peng, Qiao
    Gong, Jian
    Huo, Ji-Rong
    [J]. MOLECULAR MEDICINE REPORTS, 2016, 13 (01) : 273 - 280
  • [10] MiR-1246 and Mir-302 Are Novel Targets of Epigenetic Therapy With Dznep and SAHA in Human Cancer Cells
    Hibino, Sana
    Saito, Yoshimasa
    Muramatsu, Toshihide
    Otani, Aki
    Kasai, Yusuke
    Kimura, Masaki
    Saito, Hidetsugu
    [J]. GASTROENTEROLOGY, 2013, 144 (05) : S876 - S876