Department of Gastrointestinal Surgery, Suzhou First People's Hospital, Suzhou, China.
Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5752-5761. doi: 10.26355/eurrev_201907_18312.
To investigate the characteristics of long non-coding RNA (lncRNA) HOTAIR in colon cancer, and to further explore its function in the development of colon cancer and its potential regulatory mechanisms.
Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect HOTAIR expression in 72 colon cancer tissues along with adjacent normal tissues. Meanwhile, the relationship between HOTAIR level and colon cancer pathological parameters and patient prognosis were analyzed, respectively. QRT-PCR further verified the HOTAIR expression in colon cancer cells. Besides, knockdown and overexpression of HOTAIR models were constructed using lentivirus in HT29 and HCT-116 colon cancer cell lines. Cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EDU) and cell colony formation assays were used to analyze the effects of HOTAIR on biological function of colon cancer cell. In addition, dual luciferase reporter gene assay was performed to explore the underlying mechanisms.
QRT-PCR results showed that HOTAIR expression in colon cancer was significantly higher than that in normal tissues. The incidence of distant metastasis was higher in patients with high expression of HOTAIR while their survival rate was lower than that of patients with low HOTAIR expression. Meanwhile, cell proliferation, invasion as well as migration ability of the cells in HOTAIR knockdown group was significantly decreased than those in the negative control group. QRT-PCR results showed that mRNA levels of miR-34a and HOTAIR in colon cancer tissues were negatively correlated. Besides, luciferase reporter gene assay revealed that overexpression of miR-34a significantly attenuated the luciferase activity of the wild-type HOTAIR vector group without attenuating the mutant HOTAIR vector group (p>0.05) In addition, the recovery experiment also found a mutual regulation between HOTAIR and miR-34a, together they could affect the malignant progression of colon cancer.
HOTAIR expression was significantly increased in colon cancer, which was in association with distant metastasis and poor prognosis of colon cancer. In addition, HOTAIR may promote malignant progression of colon cancer by regulating miR-34a.
研究长链非编码 RNA（lncRNA）HOTAIR 在结肠癌中的特征，并进一步探讨其在结肠癌发展中的作用及其潜在的调控机制。
采用实时定量聚合酶链反应（qRT-PCR）检测 72 例结肠癌组织及相邻正常组织中 HOTAIR 的表达。同时，分析 HOTAIR 水平与结肠癌病理参数及患者预后的关系。qRT-PCR 进一步验证了结肠癌细胞中 HOTAIR 的表达。此外，利用慢病毒在 HT29 和 HCT-116 结肠癌细胞系中构建 HOTAIR 敲低和过表达模型。采用细胞计数试剂盒-8（CCK-8）、5-乙炔基-2'-脱氧尿苷（EDU）和细胞集落形成实验分析 HOTAIR 对结肠癌细胞生物学功能的影响。此外，还进行了双荧光素酶报告基因实验以探讨潜在的机制。
qRT-PCR 结果显示，结肠癌中 HOTAIR 的表达明显高于正常组织。HOTAIR 高表达患者的远处转移发生率较高，其生存率低于 HOTAIR 低表达患者。同时，HOTAIR 敲低组细胞的增殖、侵袭和迁移能力明显低于阴性对照组。qRT-PCR 结果显示，结肠癌组织中 miR-34a 和 HOTAIR 的 mRNA 水平呈负相关。此外，荧光素酶报告基因实验显示，过表达 miR-34a 可显著减弱野生型 HOTAIR 载体组的荧光素酶活性，但对突变型 HOTAIR 载体组无减弱作用（p＞0.05）。此外，恢复实验还发现 HOTAIR 和 miR-34a 之间存在相互调节作用，共同影响结肠癌的恶性进展。
HOTAIR 在结肠癌中表达明显增加，与结肠癌的远处转移和不良预后有关。此外，HOTAIR 可能通过调节 miR-34a 促进结肠癌的恶性进展。
