Ye Ying, Song Yanan, Zhuang Juhua, He Saifei, Ni Jing, Xia Wei
Department of Nuclear Medicine, the Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China.
Oncol Res. 2018 Oct 17;26(9):1383-1390. doi: 10.3727/096504018X15188340975709. Epub 2018 Feb 22.
Long noncoding RNA CCAL has been reported to promote tumor progression in various human cancers, including hepatocellular carcinoma, osteosarcoma, and colorectal cancer. However, the role of CCAL in papillary thyroid cancer remains largely unknown. In the present study, we found that the expression of CCAL was upregulated in papillary thyroid tumor tissues compared to adjacent normal tissues. Moreover, the expression of CCAL was positively related with papillary thyroid cancer severity and TNM stage and predicated poor prognosis. Besides, we found that knockdown of CCAL significantly inhibited papillary thyroid cancer cell proliferation, migration, and invasion in vitro and reduced tumor growth and metastasis in vivo. We found that knockdown of CCAL dramatically decreased the expression of NOTCH1 and suppressed the activation of the NOTCH1 signaling pathway. Furthermore, overexpression of NOTCH1 rescued the proliferation, migration, and invasion in papillary thyroid cancer cells. Taken together, our data indicated that CCAL promoted papillary thyroid cancer development and progression by activation of the NOTCH1 pathway, which provided a new insight on the design of therapeutic targets.
据报道,长链非编码RNA CCAL可促进包括肝细胞癌、骨肉瘤和结直肠癌在内的多种人类癌症的肿瘤进展。然而,CCAL在甲状腺乳头状癌中的作用仍 largely未知。在本研究中,我们发现与相邻正常组织相比,CCAL在甲状腺乳头状肿瘤组织中的表达上调。此外,CCAL的表达与甲状腺乳头状癌的严重程度和TNM分期呈正相关,并预示预后不良。此外,我们发现敲低CCAL可显著抑制甲状腺乳头状癌细胞在体外的增殖、迁移和侵袭,并在体内减少肿瘤生长和转移。我们发现敲低CCAL可显著降低NOTCH1的表达并抑制NOTCH1信号通路的激活。此外,NOTCH1的过表达挽救了甲状腺乳头状癌细胞的增殖、迁移和侵袭。综上所述,我们的数据表明CCAL通过激活NOTCH1途径促进甲状腺乳头状癌的发生和进展,这为治疗靶点的设计提供了新的见解。