MicroRNA-326 inhibits melanoma progression by targeting KRAS and suppressing the AKT and ERK signalling pathways

Abstract

Abstract. Melanoma is the seventh most common malignancy in females and the fifth most common cancer in males worldwide. An increasing number of studies have reported that microRNA (miRNA) dysregulation is frequently observed in various types of human cancers, including melanoma. Abnormally expressed miRNAs play an important role in melanoma formation and progression by serving as potential biomarkers and therapeutic targets. Recently, miRNA-326 (miR-326) has been reported to be differentially expressed in various types of tissues and play important roles in tumourigenesis and tumour development. However, the expression levels, biological roles and underlying mechanisms of miR-326 in melanoma remain unknown. In the present study, we demonstrated that miR-326 was significantly downregulated in melanoma tissues and cell lines. Functional assays revealed that the enforced expression of miR-326 suppressed melanoma cell proliferation and invasion and increased cell apoptosis in vitro. Using bioinformatic analysis, Kirsten rat sarcoma viral oncogene homolog (KRAS) was predicted as a potential target of miR-326. Luciferase reporter assay confirmed that miR-326 could directly target the 3'-untranslated region of KRAS. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis revealed that miR-326 upregulation decreased the KRAS expression in melanoma cells at both the mRNA and protein level. Furthermore, KRAS was upregulated in melanoma tissues and inversely correlated with miR-326 expression. In addition, the KRAS knockdown phenocopied the tumour-suppressing effects of miR-326 overexpression on melanoma cells. The restoration of the expression of KRAS markedly reversed the antitumour effects induced by miR-326 overexpression in melanoma cells. Further experiments indicated that miR-326 inactivated the AKT and ERK signalling pathways in melanoma. Collectively, these results revealed that miR-326 serves as a tumour suppressor in melanoma by targeting KRAS and regulating the AKT and ERK signalling pathways, indicating that miR-326 may be a promising therapeutic target for melanoma patients.

miR-326 inhibits the progression of papillary thyroid carcinoma by targeting MAPK1 and ERBB4

“…Moreover, miR-326 overexpression could also suppress tumorigenesis in vivo. Consistent with the existing studies, miR-326 could have an abnormal expression in various human cancers and negatively regulate the procession of tumors [33][34][35]. These findings can offer supporting evidence for the suppressive roles of miR-326 in PTC.…”

miR‑30a‑5p inhibits the proliferation, migration and invasion of melanoma cells by targeting SOX4

“…Liu et al (9) reported that miRNA-675 inhibits cell proliferation and invasion in melanoma by directly targeting metadherin. Kang et al indicated that miRNA-326 inhibits melanoma progression by targeting KRAS and suppressing the AKT and ERK signalling pathways (10). Therefore, investigation of the function and mechanism of miRNAs in the progression of melanoma is very important for melanoma intervention.…”

Tanshinone I attenuates proliferation and chemoresistance of cervical cancer in a KRAS‐dependent manner

“…Qian et al reported that the apoptosis‐inducing effect of chamaejasmine on cervical cancer cells was mediated through the inhibition of PI3K/AKT signaling pathway. In addition, previous studies indicated that KRAS inhibition markedly repressed AKT signaling pathway and cell proliferation of various tumors . To further identify the specific target of KRAS in HeLa cells, protein levels of p‐AKT and t‐AKT were evaluated, and the results demonstrated that tanshinone I repressed the activation of AKT in HeLa cells.…”