MicroRNA-379 acts as a tumor suppressor in non-small cell lung cancer by targeting the IGF-1R-mediated AKT and ERK pathways

Abstract

Lung cancer is one of the most common types of malignancy in humans and is a leading cause of cancer-related deaths among men and women worldwide. Aberrantly expressed microRNAs in non-small cell lung cancer (NSCLC) contribute to tumor occurrence and development as either tumor suppressors or promoters. MicroRNA-379 (miR‑379) is dysregulated in several types of human cancer. However, its expression pattern, role and underlying mechanism in NSCLC progression and metastasis are poorly understood. In this study, assay of reverse transcription-quantitative polymerase chain reaction showed that miR‑379 was downregulated in both NSCLC tissue and cell lines. Low miR‑379 expression in NSCLC tissues was significantly correlated with TNM stage and lymph node metastasis. In addition, functional experiments revealed that restoring the expression of miR‑379 inhibited cell proliferation, migration and invasion of NSCLC. The insulin-like growth factor receptor-1 (IGF‑1R) was identified as a direct target of miR‑379 in NSCLC. IGF‑1R was highly expressed in NSCLC tissues and inversely correlated with miR‑379 expression. Downregulation of IGF‑1R had tumor suppressive roles similar to that of miR‑379 overexpression on NSCLC cell proliferation, migration and invasion. Moreover, the upregulation of IGF‑1R effectively rescued the tumor suppressive roles induced by miR‑379 overexpression in NSCLC. The resumption of the expression of miR‑379 inhibited the activation of AKT and ERK signaling pathways in NSCLC. These findings suggested that miR‑379 acts as a tumor suppressor in NSCLC by directly targeting IGF‑1R and indirectly regulating AKT and ERK signaling pathways. miR‑379 provides novel therapeutic targets for the treatment of patients with this disease.

Downregulation of N-Acetylglucosaminyltransferase GCNT3 by miR-302b-3p Decreases Non-Small Cell Lung Cancer (NSCLC) Cell Proliferation, Migration and Invasion

“…These results suggested that GCNT3 and miR-302b-3p affect NSCLC metastasis partly via the EMT. In addition, the Erk signaling pathway has been shown to be frequently activated in numerous kinds of human cancers [43][44][45]. Aberrant activation of phosphorylated Erk1/2 induced by miRNAs has been observed in lung cancer [45][46][47].…”

“…In addition, the Erk signaling pathway has been shown to be frequently activated in numerous kinds of human cancers [43][44][45]. Aberrant activation of phosphorylated Erk1/2 induced by miRNAs has been observed in lung cancer [45][46][47]. Recent reports point out that miR-379 acts as a tumor [45], miR-7 inhibits the activation of ERK/MAPK signaling pathway by down-regulating FAK expression [46], and miR-622 overexpression decreases invasion in lung tumor cells by inhibiting HIF-1alpha via inactivation of ERK signaling in A549 cell [47].…”

“…Aberrant activation of phosphorylated Erk1/2 induced by miRNAs has been observed in lung cancer [45][46][47]. Recent reports point out that miR-379 acts as a tumor [45], miR-7 inhibits the activation of ERK/MAPK signaling pathway by down-regulating FAK expression [46], and miR-622 overexpression decreases invasion in lung tumor cells by inhibiting HIF-1alpha via inactivation of ERK signaling in A549 cell [47]. Consistent with these findings, we found that the p-Erk level was significantly decreased in response to GCNT3 silencing or miR-302b-3p overexpression in XWLC and NCI-H292 cells, suggesting that the effect of the miR-302b-3p/GCNT3 signaling pathway in NSCLC may depend on the activation of p-Erk.…”

Circulating Exosomal MicroRNAs as Diagnostic and Prognostic Biomarkers in Patients with Diffuse Large B-cell Lymphoma

“…Scholars further validated the up-regulated expression level of miR-379-5p in cell line model and speculated the translocation of miR-379-5p from cancer cells to circulation might contribute to the high-regulation of miR-379-5p in circulation exosomal samples (34). Similar conditions were also reported in lung cancer (35,36). This suggested the profiling of miRNAs in circulating exosome may have a great difference with those in tissue or blood.…”

Qingjie Fuzheng granules inhibit colorectal cancer cell growth by the PI3K/AKT and ERK pathways

“…The pathogenic mechanisms underlying the development of cancer, including CRC, are heterogeneous and regulated by multiple signaling pathways, including PI3K/AKT and ERK[25,26]. Previous studies have reported that the PI3K/AKT and ERK signaling pathways regulate cell growth, apoptosis and metastasis[46]. As one of the important intracellular signal transduction pathways, PI3K/AKT signaling has been reported to play important roles in cell survival, apoptosis and metastasis [47].…”