MicroRNA-27a directly targets KRAS to inhibit cell proliferation in esophageal squamous cell carcinoma

Abstract

MicroRNAs (miRNAs) are a type of small non-coding RNA that negatively regulate gene expression levels by binding to the 3′-untranslated region of specific target mRNAs. To investigate the role of miR-27a in esophageal squamous cell carcinoma (ESCC), TargetScan software was used to predict the target gene of miR-27a. Kirsten rat sarcoma viral oncogene homolog (KRAS), which has been implicated as a regulator of cell proliferation, differentiation and transformation, was identified as a potential target gene of miR-27a and, thus, was the focus of the present study. Luciferase activity in cells transfected with miR-27a mimics was 48% lower when compared with that of the miRNA-negative control. Furthermore, expression levels of the K-ras protein were reduced by ≤50% in cells cotransfected with an expression vector containing miR-27a and miR-27a binding sequences, when compared with the control. The expression level of miR-27a was significantly lower in ESCC cell lines and tissues when compared with healthy esophageal epithelial cells and tissues. However, the expression level of the target gene, KRAS was upregulated and ESCC cell proliferation was significantly inhibited following miR-27a mimic or small interfering K-ras transfection. In conclusion, the present study demonstrated that the expression level of miR-27a was low in ESCC and that miR-27a directly targets the KRAS gene, resulting in inhibited cell proliferation in esophageal cancer.

miR-200c inhibits breast cancer proliferation by targeting KRAS

“…The genetic mutation of intracellular effectors that are involved in GTPase-related signaling pathways usually have an effect on the response of the targeted therapy [ 20 ]. Recently, KRAS mutations have been reported to be involved in human cancer, including nasopharyngeal carcinoma [ 21 ], ovarian cancer [ 22 ], lung cancer [ 23 ], pancreatic cancer [ 24 ], oral squamous cell carcinoma [ 25 ], esophageal squamous cell carcinoma [ 26 ], colorectal cancer [ 27 ], breast cancer [ 28 ] and so on.…”

Targeting oncogenic PLCE1 by miR-145 impairs tumor proliferation and metastasis of esophageal squamous cell carcinoma

“…MiRNA are aberrantly expressed in various cancers and function as a novel class of oncogenes or tumor suppressor genes depending on their targets [ 26 ]. In ESCC, the aberrant expressions level of miRNAs, such as miR-27a, miR-9, miR-335, and miR-183, regulate tumor cell growth, apoptosis, migration, and invasion by targeting proteins involved in these cellular pathways [ 27 – 30 ]. Thus far, miRNAs that selectively regulate PLCE1 in ESCC have not been identified.…”

Evaluation of miR-27a, miR-181a, and miR-570 Genetic Variants with Gallbladder Cancer Susceptibility and Treatment Outcome in a North Indian Population

“…miR-27a and miR-181a have several cancerous targeted genes. Recently it was reported that miR-27a, miR-181 targets the kras gene and deregulates its expression [40,41]. Mutations in TP53 and the KRAS gene are the most repeated molecular alterations related to GBC.…”