长链非编码 RNA DMTF1v4 在结肠癌发生中的功能与机制研究。
Study on the function and mechanism of long non-coding RNA DMTF1v4 in the occurrence of colon cancer.
机构信息
Department of Gastrointestinal Surgery, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, P.R. China.
出版信息
Eur Rev Med Pharmacol Sci. 2018 Jun;22(12):3779-3788. doi: 10.26355/eurrev_201806_15260.
OBJECTIVE
To investigate the expression of long non-coding RNA (lncRNA) DMTF1v4 in colon cancer, and the relationship between its expression and disease occurrence.
MATERIALS AND METHODS
Human colon cancer tissues and para-carcinoma tissues were harvested. The expression of lncRNA DMTF1v4 was measured by semi-quantitative PCR. The expression of DMTF1v4 in HT-29 colon cancer cells was downregulated using siRNA, and the effect of its downregulation on cell growth was determined by MTT assay and plate clone assay. The effect of DMTF1v4 downregulation on colon cancer cell migration was determined using a transwell assay and scratch wound assay. The effect of DMTF1v4 on colon cancer cell apoptosis was determined using Annexin V/PI double-staining. The changes in p-ERK, p-JNK, and p-p38 were measured by Western blot. HT-29 cells with downregulated DMTF1v4 expression were used to establish the subcutaneous heterotopic transplantation tumor model in nude mice to study the effect of DMTF1v4 on tumor growth in animals.
RESULTS
Compared with para-carcinoma tissue, lncRNA DMTF1v4 in colon cancer tissue was highly expressed (p<0.001). Downregulating lncRNA DMTF1v4 in HT-29 cells showed that lncRNA DMTF1v4 promotes cell proliferation and migration, and suppresses apoptosis (p<0.05). The effect of lncRNA DMTF1v4 on the ERK/MAPK signaling pathway was evaluated. The expression of p-ERK, p-JNK, and p-p38 was increased significantly compared with the control group (p<0.01). The effect of downregulating DMTF1v4 on tumor growth in animals showed that tumor growth in nude mice was decreased, and the expression of apoptosis-related proteins was increased (p<0.01).
CONCLUSIONS
The expression of lncRNA DMTF1v4 is elevated in colon cancer tissues; lncRNA DMTF1v4 promotes colon cancer cell proliferation and migration, and inhibits apoptosis by downregulating the expression of p-ERK, p-JNK, and p-p38, thus affecting the progression of colon cancer. This will provide a basis for the development of new clinical treatments for colon cancer.
目的
研究长链非编码 RNA（lncRNA）DMTF1v4 在结肠癌中的表达及其与疾病发生的关系。
材料与方法
收集人结肠癌组织及癌旁组织，采用半定量 PCR 检测 lncRNA DMTF1v4 的表达，采用 siRNA 下调 HT-29 结肠癌细胞中 DMTF1v4 的表达，MTT 法和平板克隆实验检测其下调对细胞生长的影响，Transwell 实验和划痕实验检测其对结肠癌细胞迁移的影响，Annexin V/PI 双染法检测其对结肠癌细胞凋亡的影响，Western blot 法检测 DMTF1v4 下调对 ERK/MAPK 信号通路中 p-ERK、p-JNK 和 p-p38 表达的影响。采用下调 DMTF1v4 表达的 HT-29 细胞建立裸鼠皮下异位移植瘤模型，研究 DMTF1v4 对动物肿瘤生长的影响。
结果
与癌旁组织相比，结肠癌组织中 lncRNA DMTF1v4 高表达（p<0.001）。下调 HT-29 细胞中的 lncRNA DMTF1v4 后，lncRNA DMTF1v4 促进细胞增殖和迁移，抑制细胞凋亡（p<0.05）。评价 lncRNA DMTF1v4 对 ERK/MAPK 信号通路的影响，与对照组相比，p-ERK、p-JNK 和 p-p38 的表达明显增加（p<0.01）。下调 DMTF1v4 对动物肿瘤生长的影响表明，裸鼠肿瘤生长减少，凋亡相关蛋白表达增加（p<0.01）。
结论
lncRNA DMTF1v4 在结肠癌组织中表达上调；lncRNA DMTF1v4 通过下调 p-ERK、p-JNK 和 p-p38 的表达促进结肠癌细胞增殖、迁移，抑制细胞凋亡，从而影响结肠癌的进展。这为结肠癌的临床治疗提供了新的依据。
Zotero 插件