Chen Rui, Xia Wenjia, Wang Xiaoxiao, Qiu Mantang, Yin Rong, Wang Siwei, Xi Xiaoxiang, Wang Jie, Xu Youtao, Dong Gaochao, Xu Lin, De Wei
Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, Jiangsu 210009, P.R. China.
Department of Thoracic Surgery, The Fourth Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
Oncol Lett. 2018 Apr;15(4):5071-5080. doi: 10.3892/ol.2018.7968. Epub 2018 Feb 6.
Esophageal cancer is one of the most common types of malignant tumors located within the digestive system, with >50% of esophageal cancer cases worldwide occurring in China. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are frequently dysregulated in cancer; however, few lncRNAs have been characterized in esophageal squamous cell carcinoma (ESCC). In the present study, a novel lncRNA, SET-binding factor 2 (SBF2) antisense RNA1 (SBF2-AS1) was exhibited in ESCC. Expression levels of SBF2-AS1 in ESCC and adjacent non-cancerous tissues were detected using the reverse transcription-quantitative polymerase chain reaction. SBF2-AS1 was knocked down, and proliferation, migration, invasion, apoptosis and the cell cycle were examined in ESCC cells. Results identified that SBF2-AS1 was significantly upregulated in ESCC compared with adjacent non-cancerous tissues (fold increase, 8.82; P=0.023). The SBF2-AS1 expression level was significantly increased in patients who had a smoking (9.927 vs. 4.507; P=0.030) and/or drinking (10.938 vs. 4.232; P=0.032) history. Patients with a large tumor size exhibited increased SBF2-AS1 expression (≥4 vs. <4 cm, 14.898 vs. 5.435; P=0.018). Patients with advanced ESCC exhibited increased upregulation of SBF2-AS1 [tumor-node-metastasis (TNM) I-II vs. TNM III-IV, 1.302 vs. 15.475; P<0.01]. SBF2-AS1 was also silenced using small interfering RNA. Cell proliferative and invasive ability were significantly inhibited (P<0.05) following SBF2-AS1 silencing, the cell cycle was arrested in the G phase; however, there was no significant difference in the proportion of apoptotic cells. Gene Set Enrichment Analysis revealed that genes associated with cell cycle biological processes, including the cancer suppressor gene cyclin-dependent kinase 1A (CDKN1A), were significantly associated with SBF2-AS1 in ESCC tissues. Further validation confirmed that CDKN1A expression levels were increased in ECA-109 cells following SBF2-AS1 silencing. The results of the present study demonstrate that SBF2-AS1 is significantly upregulated in ESCC, and that silencing of SBF2-AS1 inhibits the proliferative and invasive ability of ESCC cells. SBF2-AS1 may be a novel biomarker and therefore a potential therapeutic target for ESCC.
食管癌是消化系统中最常见的恶性肿瘤类型之一，全球超过50%的食管癌病例发生在中国。最近的研究表明，长链非编码RNA（lncRNA）在癌症中经常失调；然而，很少有lncRNA在食管鳞状细胞癌（ESCC）中得到表征。在本研究中，一种新的lncRNA，SET结合因子2（SBF2）反义RNA1（SBF2-AS1）在ESCC中被发现。使用逆转录定量聚合酶链反应检测ESCC组织和相邻非癌组织中SBF2-AS1的表达水平。敲低SBF2-AS1，并检测ESCC细胞的增殖、迁移、侵袭、凋亡和细胞周期。结果发现，与相邻非癌组织相比，ESCC中SBF2-AS1显著上调（增加倍数为8.82；P=0.023）。有吸烟（9.927对4.507；P=0.030）和/或饮酒（10.938对4.232；P=0.032）史的患者SBF2-AS1表达水平显著升高。肿瘤较大的患者SBF2-AS1表达增加（≥4 cm对<4 cm，14.898对5.435；P=0.018）。晚期ESCC患者SBF2-AS1上调增加[肿瘤-淋巴结-转移（TNM）I-II期对TNM III-IV期，1.302对15.475；P<0.01]。还使用小干扰RNA使SBF2-AS1沉默。SBF2-AS1沉默后，细胞增殖和侵袭能力显著受到抑制（P<0.05），细胞周期停滞在G期；然而，凋亡细胞比例没有显著差异。基因集富集分析显示，与细胞周期生物学过程相关的基因，包括抑癌基因细胞周期蛋白依赖性激酶1A（CDKN1A），在ESCC组织中与SBF2-AS1显著相关。进一步验证证实，SBF2-AS1沉默后，ECA-109细胞中CDKN1A表达水平升高。本研究结果表明，ESCC中SBF2-AS1显著上调，沉默SBF2-AS1可抑制ESCC细胞的增殖和侵袭能力。SBF2-AS1可能是一种新的生物标志物，因此是ESCC的潜在治疗靶点。
