Abstract
Downregulation of microRNA-200b (miR-200b) has been identified in a range of cancers, yet the specific mechanisms whereby it influences lung cancer growth require further exploration. We determined that lung cancer patient tumor samples exhibit decreased miR-200b expression, and we further found this miRNA to inhibit tumor growth via interfering with ERK1/2 and AKT signaling, targeting p70S6K1 to suppress HIF-1α expression. This miRNA further rendered H1299 cells more sensitive to cisplatin while impairing their proliferative and invasive potential through its ability to target and inhibit the activity of p70S6K1. These results were further confirmed in a murine xenograft model in which miR-200b also inhibited the growth of tumor and suppressed p70S6K1, p-AKT, p-ERK1/2, and HIF-1α expression. These findings clearly demonstrate a role for miR-200b in suppressing lung cancer development, making it a potentially relevant target for future diagnostic and therapeutic interventions.
Highlights
Lung cancers, of which up to 85% are non-small cell lung cancers (NSCLCs), remain one of the deadliest forms of cancer globally [1], with most NSCLC patients not being diagnosed until the disease is relatively advanced, resulting in almost 9 in 10 patients dying due to complications of tumor progression and metastasis [2]
The miR-200 family is a group of miRNAs with an overlapping set of target genes and an identical seed sequence, with these miRNAs having been implicated in regulation of epithelial-to-mesenchymal transition (EMT) in tumor cells [9]
We further explored the role of miR-200b in the growth and functionality of these lung cancer cells, identifying its target genes and exploring the effects of overexpression of this miRNA on lung cancer cell growth and chemoresistance
Summary
Of which up to 85% are non-small cell lung cancers (NSCLCs), remain one of the deadliest forms of cancer globally [1], with most NSCLC patients not being diagnosed until the disease is relatively advanced, resulting in almost 9 in 10 patients dying due to complications of tumor progression and metastasis [2]. This disease has just a 17% 5-year survival rate [3, 4].
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