Down-regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2

Abstract

BackgroundColorectal cancer (CRC) is the most common digestive system malignancy. The molecular events involved in the development and progression of CRC remain unclear. Recently, more and more evidences have showed that deregulated miRNAs participate in colorectal carcinogenesis.MethodsThe expression levels of miR-138 were first examined in CRC cell lines and tumor tissues by real-time PCR. The in vitro and in vivo functional effects of miR-138 were examined further. Luciferase reporter assays were conducted to confirm the targeting associations. Kaplan-Meier analysis and log-rank tests were performed to estimate the overall survival and disease free survival rate.ResultsmiR-138 was found to be down-regulated in human colorectal cancer tissues and cell lines. Ectopic expression of miR-138 resulted in a dramatic inhibition of CRC migration and invasion in vitro and in vivo. Twist basic helix-loop-helix transcription factor 2 gene (TWIST2) was identified as one of the functional target. Restoration of miR-138 resulted in a dramatic reduction of the expression of TWIST2 at both mRNA and protein levels by directly targeting its 3′-untranslated region (3′UTR). Up-regulation of TWIST2 was detected in CRC tumors compared with adjacent normal tissues (P < 0.001) and is inversely correlated with miR-138 expression. We also identified that down-regulation of miR-138 was associated with lymph node metastasis, distant metastasis, and always predicted poor prognosis.ConclusionThese data highlight a pivotal role for miR-138 in the regulation of CRC metastasis by targeting TWIST2, and suggest a potential application of miR-138 in prognosis prediction and CRC treatment.

MicroRNA‑138 suppresses cell proliferation and invasion of renal cell carcinoma by directly targeting SOX9

“…Downregulation of miR-138 has been identified in several cancer types, including breast cancer (21), bladder cancer (22), larynx carcinoma (23), colorectal cancer (24,25), non-small cell lung cancer (26,27), oral squamous cell carcinoma (28), gallbladder carcinoma (29), pancreatic cancer (30), hepatocellular carcinoma (31) and glioblastoma (32). More significantly, miR-138 expression levels were observed to be correlated with clinicopathological features of cancer patients.…”

“…Sun et al noted that miR-138 targeted zinc finger E-box-binding homeobox 2 to suppress bladder cancer invasion and metastases (22). Long et al demonstrated that inhibition of miR-138 in colorectal cancer cells resulted in a significant reduction of migration and invasion capacity by directly targeting TWIST2 (25). In non-small cell lung cancer, miR-138 decreased cell proliferation, migration in vitro and tumor growth in vivo, and increased cisplatin sensitivity through targeting multiple genes, including G protein-coupled receptor kinase interacting ArfGAP 1 (GIT1), semaphorin 4C, cyclin D3, Glucose regulated protein 124 (GRP124), enhancer of zeste homolog 2 and pyruvate dehydrogenase kinase 1 (26,(33)(34)(35).…”

MicroRNA‑138 targets SP1 to inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells

“…Xu et al (35) revealed that miR-138 overexpression suppressed oral squamous cell carcinoma (36) and gallbladder carcinoma cell growth. Yang et al (26) found that miR-138 expression resulted in a significant inhibition of colorectal cancer cell migration and invasion in vitro and in vivo. In ovarian cancer, miR-138 overexpression repressed cancer cell invasion and metastasis (24).…”

MicroRNA-138 inhibits proliferation, migration and invasion through targeting hTERT in cervical cancer

“…miR-138, a family of microRNA precursors, has been reported to function as a tumor suppressor in a variety of human cancers, including renal carcinoma (13), non-small lung cancer (14), colorectal cancer (15), neuroblastoma (16), esophageal squamous cell carcinoma (17), nasopharyngeal carcinoma (18) and hepatocellular carcinoma (19). However, the role and the molecular mechanisms of miR-138 in cervical remain unclear.…”