Lee Shiao-Pieng, Hsieh Pei-Ling, Fang Chih-Yuan, Chu Pei-Ming, Liao Yi-Wen, Yu Chuan-Hang, Yu Cheng-Chia, Tsai Lo-Lin
School of Dentistry, National Defense Medical Center, Taipei 11490, Taiwan.
Department of Dentistry, Tri-Service General Hospital, Taipei 11490, Taiwan.
Cancers (Basel). 2020 Apr 26;12(5):1073. doi: 10.3390/cancers12051073.
Accumulating studies have indicated that long non-coding RNAs (lncRNAs) participate in the regulation of cancer stem cells (CSCs), which are crucial in tumor initiation, metastasis, relapse, and therapy resistance. In the current study, RT-PCR analysis was employed to evaluate the expression of LINC00963 in tumor tissues and oral CSCs. Stemness phenotypes and the expression of CSCs markers in oral cancer cells transfected with sh-LINC00963 were examined. Our results showed that the expression of the lncRNA LINC00963 was up-regulated in oral cancer tissues and CSCs. We found that the downregulation of LINC00963 inhibited CSC hallmarks, such as migration, invasion and colony formation capacity. Moreover, suppression of LINC00963 reduced the activity of stemness marker ALDH1, the percentage of self-renewal, chemoresistance and the expression of multidrug-resistance transporter ABCB5. Most importantly, we demonstrated that knockdown of LINC00963 decreased self-renewal, invasion and colony formation ability via ABCB5. Analysis of TCGA (the Cancer Genome Atlas) datasets suggested that the level of LINC00963 was positively correlated with the expression of the cancer stemness markers (Sox2 and CD44) and drug resistance markers (ABCG2 and ABCB5). Altogether, our results showed that suppression of LINC00963 may be beneficial to inhibit chemoresistance and cancer relapse in oral cancer patients.
越来越多的研究表明，长链非编码RNA（lncRNAs）参与癌症干细胞（CSCs）的调控，而癌症干细胞在肿瘤的起始、转移、复发和治疗耐药性方面至关重要。在本研究中，采用逆转录聚合酶链反应（RT-PCR）分析来评估LINC00963在肿瘤组织和口腔癌干细胞中的表达。检测了用sh-LINC00963转染的口腔癌细胞的干性表型和癌症干细胞标志物的表达。我们的结果显示，lncRNA LINC00963在口腔癌组织和癌症干细胞中表达上调。我们发现，LINC00963的下调抑制了癌症干细胞的特征，如迁移、侵袭和集落形成能力。此外，抑制LINC00963降低了干性标志物醛脱氢酶1（ALDH1）的活性、自我更新百分比、化学抗性以及多药耐药转运蛋白ABCB5的表达。最重要的是，我们证明敲低LINC00963通过ABCB5降低了自我更新、侵袭和集落形成能力。对癌症基因组图谱（TCGA）数据集的分析表明，LINC00963的水平与癌症干性标志物（Sox2和CD44）以及耐药标志物（ABCG2和ABCB5）的表达呈正相关。总之，我们的结果表明，抑制LINC00963可能有助于抑制口腔癌患者的化学抗性和癌症复发。
