MiR‐216a‐3p inhibits colorectal cancer cell proliferation through direct targeting COX‐2 and ALOX5

Abstract

Colorectal Cancer (CRC) is a most common digestive system malignant tumor. Despite recent advance in CRC treatment, searching for efficient biomarker and individual treatment therapy remains an urgent need. Cyclooxygenase-2 (COX-2) plays a critical role in the development and progression of CRC. In addition, shunting of arachidonic acid metabolism to the 5-lipoxygenase (ALOX5, 5-LO) pathway has also been reported to be implicated in the CRC pathogenesis. Cancer cell viability is promoted by ALOX5 through several mechanisms that are similar to those of COX-2. In recent years, it has been widely recognized that through inhibition of target genes, miRNAs can exert both oncogenic and tumor suppressive functions, depending on circumstances. In the present study, we screened for candidate microRNAs (miRNAs) which were predicted to regulate COX-2 and ALOX5 by online tools. Among the candidate miRNAs, miR-216a-3p expression was down-regulated in CRC tissues and cell lines; a higher miR-216a-3p expression was correlated with longer overall survival in patients with CRC. Moreover, ectopic miR-216a-3p expression significantly suppressed CRC cell proliferation. Using luciferase reporter gene, real-time PCR, and western blot assays, we confirmed the miR-216a-3p regulation of COX-2 and ALOX5 through direct targeting; further verified that miR-216a-3p could inhibit COX-2 and ALOX5 expression in CRC cells, thus to affect CRC cell proliferation. Taken together, miR-216a-3p presents a novel target of CRC treatment; rescuing miR-216a-3p expression in CRC might be a promising strategy for CRC treatment.

MiR‐216a‐3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A‐mediated YAP signaling

“…(d) The effect of miR-216a-3p overexpression on YAP/TAZ-mediated transcriptional activity was monitored by a luciferase reporter assay. *p < .05 versus NC mimics colorectal cancer cells through the downregulation of cyclooxygenase-2 and 5-lipoxygenase (Wang et al, 2018). In gastric cancer cells, upregulation of miR-216a-3p resulted in an inhibitory effect on the proliferation, migration, and invasion via targeting runtrelated transcription factor 1 (Wu et al, 2018).…”

Microarray profile of circular RNAs identifies hsa_circ_0014130 as a new circular RNA biomarker in non-small cell lung cancer

“…It have been found that miR-216a-3p was significantly reduced in pancreatic ductal adenocarcinoma and could affect colorectal cancer cell proliferation by inhibiting COX-2 and ALOX5 expression 29 , 30 . miR-493-5p has been found to be deregulated in several tumours, such as breast cancer and myeloid leukemia 31 , 32 .…”

Circular RNA profile of infantile hemangioma by microarray analysis

“…Among them, miR-137 targeted by circRNA_100933, has been reported to act as tumor suppressor in various tumors [ 41 , 42 ]. Previous study demonstrated that miR-216a-3p, one of the target miRNAs of circRNA_104310, inhibited gastric and colorectal cancer cell proliferation and migration [ 43 , 44 ]. Moreover, hsa-520d-3p and hsa-miR-520a-5p targeted by hsa_circRNA_001654 and hsa_miR-518f-3p targeted by hsa_circRNA_102116 were implicated as biomarkers in IH [ 14 ], suggesting the potency of circRNAs as biomarker candidates in IH.…”