Long non-coding RNA MIAT promotes growth and metastasis of colorectal cancer cells through regulation of miR-132/Derlin-1 pathway

Zhaoxia Liu,Zhining Fan,Yan Li,Hai Wang,Dongming Su,Ye Hong,Hongwei Cai

doi:10.1186/s12935-017-0477-8

Abstract

ObjectiveRecently, 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.MethodsReal-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.ResultsIn 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.ConclusionsOur data indicated that highly expressed MIAT was an oncogenic lncRNA that promoted the growth and metastasis of CRC through miR-132/Derlin-1 axis.

Highlights

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancy worldwide, with over one million newly diagnosed cases every year [1]
LncRNA‐MIAT expression was up‐regulated in CRC tissues and cell lines Real-time PCR analysis was used to determine lncRNAMIAT expression in 30 pairs of CRC tissue and matched adjacent normal tissue samples
Our results showed that MIAT expression was significantly increased in CRC cells (Fig. 1b)

Summary

Introduction

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancy worldwide, with over one million newly diagnosed cases every year [1]. The 5-year survival rate in CRC patients with early-stage is over 90% but decrease to less than 10% in patients with advanced disease and metastasis [2]. It is of great importance to make clear the key molecules closely associated with proliferation and metastasis of CRC cells. In CRC, miR-132 functions as a tumor suppressor. The decreased miR-132 level was observed in CRC tissues and was associated with tumor size, TNM stage, distant metastasis and poor survival in CRC patients [5, 6]. Further study showed that over-expression of miR-132 could inhibit EMT and invasion, while downregulation of miR-132 increased CRC cell motility and EMT progression [7]. MiR-132 might serve as a prognostic indicator and therapeutic candidate in CRC patients

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Discussion

Conclusion