Antagomir-1290 suppresses CD133+ cells in non-small cell lung cancer by targeting fyn-related Src family tyrosine kinase

Abstract

Cancer stem-like cells (CSLCs) are involved in cancer initiation, development, and metastasis, and microRNAs (miRNAs) play pivotal roles in regulating CSLCs. miRNA-based therapeutic strategy associated with CSLCs might promise potential new therapeutic approaches. In the present study, we found that miR-1290 was increased in CD133(+) cells. Antagomir-1290 significantly suppressed tumor volume and weight initiated by CD133(+) cells in vivo. Furthermore, antagomir-1290 significantly inhibited the proliferation, clonogenicity, invasion, and migration of CD133(+) cells by targeting fyn-related Src family tyrosine kinase. These findings provide insights into the clinical prospect of miR-1290-based therapies for non-small cell lung cancer.

Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling

“…Previous reports have indicated that CrkL functions as an adaptor protein that links Src and C3G proteins (31,32). Increased activity of Src is a frequent occurrence in many types of human cancer, and there is growing evidence of a prominent role of Src in invasion and in other tumor progression-related events, such as the epithelial-mesenchymal transition and development of metastasis (33–35). Thus, the present study assessed the level of Src phosphorylation in CrkL-overexpressing HeLa and CaSki cell lines, and determined that CrkL transfection significantly upregulated Src phosphorylation, suggesting that Src may be involved in CrkL-induced cell invasion.…”

Multidrug-Resistance Related Long Non-Coding RNA Expression Profile Analysis of Gastric Cancer

“…Further investigation showed that some protein-coding genes involved in the drug-resistance phenotype and development of malignant tumors maybe were cis-regulated by correlated lncRNAs. For example, ABCB1(ATP-binding cassette, sub-family B (MDR/TAP), member 1, P-glycoprotein(P-gp) coding gene), located 400Kb upstream of lncRNA MRUL (NR_024549: MDR-related and up-regulated lncRNA), was significantly up-regulated through a potential enhancement-like role played by MRUL and promoted drug-resistance phenotype of SGC7901/ADR and SGC7901/VCR cells[ 33 ]; ADAM22, a candidate gene for malignant transformation of ovarian endometriosis[ 48 ], was correlated with lncRNA AL133090 in a exon sense-overlapping way; PLCG1 was correlated with lncRNA AK021471 in a intron sense-overlapping way and recurrent mutations in PLCG1 was identified in angiosarcomas[ 49 ]; FYN was correlated with lncRNA AK AK090692 in a intron sense-overlapping way and antagomir-1290 suppresses CD133(+) cells in non-small cell lung cancer by targeting fyn-related Src family tyrosine kinase[ 50 ], etc.…”

Understanding the cellular roles of Fyn-related kinase (FRK): implications in cancer biology

“…Furthermore, a recent study on cancer stem-like cells (CSLCs) derived from the A549 non-small cell lung cancer cell (NSCLC) line identified miRNA 1290 as a repressor of FRK [65]. Accordingly, the miRNA 1290 antagonist, antagomir-1290, was shown to increase endogenous FRK protein levels in these cells.…”

“…Silencing FRK in the A549-derived CSLCs resulted in increased anchorage-independent growth as well as migratory and invasive properties. Additionally, it was noted that antagomir-1290 not only enhanced FRK expression but also PTEN protein levels which inversely correlated with AKT activation (pS473/pT308) [65]. Therefore, as with breast cancer, it is likely that FRK may exert potential tumour-suppressive effects in lung cancer-derived CCLSCs, partially, through stabilizing the tumour-suppressor PTEN and negatively regulating AKT activation.…”