Liu Zhaoxia, Wang Hai, Cai Hongwei, Hong Ye, Li Yan, Su Dongming, Fan Zhining
1Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
2Department of Gastroenterology, Affiliated Nanhua Hospital, University of South China, Hengyang, China.
Cancer Cell Int. 2018 Apr 16;18:59. doi: 10.1186/s12935-017-0477-8. eCollection 2018.
Recently, long non-coding RNA (lncRNA) MIAT has been demonstrated as an oncogenic gene in several types of cancer. However, the role and mechanism of MIAT in colorectal cancer (CRC) have not been investigated.
Real-time PCR was used to measure MIAT expression in CRC tissues and cells. Small interfering RNA specific for MIAT (si-MIAT) was used to down-regulate MIAT expression in CRC cells. The interaction of MIAT and miR-132 was measured by RNA pull-down assay. The effect of si-MIAT on CRC cells apoptosis and metastasis were measured by flow cytometry assay, invasion and migration assay, respectively.
In present study, we found that MIAT was highly expressed in CRC tissues and cells. MIAT knockdown inhibited proliferation, migration and invasion and enhanced apoptosis of CRC cells. Further, we demonstrated that MIAT acted as a competing endogenous RNA for miR-132, antagonized its functions, and resulted in the de-repression of its target gene Derlin-1, which acted as an oncogene in promoting growth and metastasis of CRC cells. In LOVO and SW480 cells with si-MIAT, miR-132 inhibitor resulted in an increase of cell proliferation, migration and invasion and a decrease of cell apoptosis, which was partially abolished by transfection of Derlin-1 shRNA.
Our data indicated that highly expressed MIAT was an oncogenic lncRNA that promoted the growth and metastasis of CRC through miR-132/Derlin-1 axis.
最近，长链非编码RNA（lncRNA）MIAT已被证明在几种类型的癌症中是一种致癌基因。然而，MIAT在结直肠癌（CRC）中的作用和机制尚未得到研究。
采用实时荧光定量PCR检测CRC组织和细胞中MIAT的表达。使用针对MIAT的小干扰RNA（si-MIAT）下调CRC细胞中MIAT的表达。通过RNA下拉试验检测MIAT与miR-132的相互作用。分别通过流式细胞术检测、侵袭和迁移试验检测si-MIAT对CRC细胞凋亡和转移的影响。
在本研究中，我们发现MIAT在CRC组织和细胞中高表达。敲低MIAT可抑制CRC细胞的增殖、迁移和侵袭，并增强其凋亡。此外，我们证明MIAT作为miR-132的竞争性内源性RNA，拮抗其功能，并导致其靶基因Derlin-1的去抑制，Derlin-1作为一种癌基因促进CRC细胞的生长和转移。在转染si-MIAT的LOVO和SW480细胞中，miR-132抑制剂导致细胞增殖、迁移和侵袭增加，细胞凋亡减少，而转染Derlin-1 shRNA可部分消除这种作用。
我们的数据表明，高表达的MIAT是一种致癌lncRNA，通过miR-132/Derlin-1轴促进CRC的生长和转移。
