Down-Regulation of microRNA-132 is Associated with Poor Prognosis of Colorectal Cancer

Abstract

BackgroundGiven the role of microRNA in colorectal cancer (CRC) progression, we explored the association between microRNA (miRNA) expression and CRC-related prognosis.Methods Three types of tissue samples (primary CRC lesions without liver metastasis, primary lesions with liver metastasis, and liver metastatic tissues) were used for miRNA profiling to identify differentially expressed miRNA. Quantitative real-time PCR was used to examine miRNA expression in CRC cells and in tumor tissues.Results MiR-132 was significantly down-regulated in primary CRC tissues with liver metastasis and liver metastatic lesions compared to primary lesions without liver metastasis. Multivariate analysis for overall survival indicated that low miR-132 expression was an independent prognostic factor for CRC patients (overall survival P = 0.040, disease-free survival P = 0.015). Ectopic expression of miR-132 significantly inhibited cell proliferation and cell invasion. The luciferase reporter assay revealed that anoctamin 1 (ANO1) was a direct target of miR-132. Kaplan–Meier survival curves showed that high ANO1 expression was a significant prognostic factor for overall survival of patients with CRC (P = 0.0344).ConclusionsDown-regulation of miR-132 is associated with poor prognosis in CRC. ANO1 could be one of the crucial targets of miR-132 in CRC.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-016-5133-3) contains supplementary material, which is available to authorized users.

Identification of microRNA-487b as a negative regulator of liver metastasis by regulation of KRAS in colorectal cancer

“…Our group also reported that miRNA-132 was related to liver metastasis of CRC and targets anoctamin 1 (ANO1) (16). In an effort to identify another novel miRNA related to liver metastasis, we focused on miR-487b that significantly decreased in liver metastatic lesions as compared to primary tumors without metastasis.…”

“…Luciferase activity was measured using Dual Luciferase Reporter assay system (Promega), as described previously (16,23). Briefly, the cell extracts were prepared by rinsing each plate twice with PBS and lysing the cells in Passive Lysis buffer (Promega).…”

“…As a testing cohort, we used microarray data that were previously registered in the NCBI Gene Expression Omnibus database available through GEO with accession number GSE72199, consisting of tumor tissues derived from 36 patients: 16 primary CRC tumors with stage II and III disease without metastasis, 12 primary CRC tumors with simultaneous liver metastasis (stage IV), and 8 liver metastatic lesions of CRC (16). Consequently, 38 miRNAs that showed significantly differential expression with fold change >2.0 in microarray analyses were identified by comparison between primary tumors without metastasis and liver metastatic lesions (Table II).…”

“…We reported that miRNA-132 was downregulated in the liver metastasis-related samples, and that this miRNA was associated with better prognosis in CRC (16). In this study, we aimed at identifying another novel miRNA that was aberrantly expressed in liver metastasis, using the microarray data.…”

Overexpression of leucine‐rich α2‐glycoprotein‐1 is a prognostic marker and enhances tumor migration in gastric cancer

“…The cell invasion assay was carried out using Transwell inserts with 8-lm pores (BD Biosciences, San Jose, CA, USA), based on the manufacturer's protocol and previous reports. (26,27) Cells were seeded into inserts for 24-well plates at 4 9 10 4 cells per insert in serum-free medium and then transferred to wells filled with the culture medium containing 10% FBS. After 24 h incubation, non-invading cells on the top of the membrane were removed by cotton swabs.…”