miR-491-5p suppresses cell growth and invasion by targeting Notch3 in nasopharyngeal carcinoma

Abstract

MicroRNAs (miRNAs) have critical roles in the progression of nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in Southern China. miR-491-5p has been implicated in multiple types of cancer; however, its biological role and underlying mechanism in NPC have not been fully explored. In the present study, we found that miR-491-5p was downregulated in NPC tissues and cell lines compared with the corresponding normal counterparts. Overexpression of miR-491-5p significantly inhibited cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Using miRNA target prediction algorithms and reporter assays, we showed that miR-491-5p suppressed Notch3 expression both at the mRNA and protein level through directly targeting the 3' untranslated region (3'-UTR) of Notch3 mRNA. Overexpression of Notch3 significantly reversed the tumor-suppressive effects of miR‑491-5p. Taken together, the present study reveals a mechanistic link between miR-491-5p and Notch3 in the pathogenesis of NPC and that miR-491-5p has potential as a therapeutic target for NPC.

Knockdown of long non‐coding RNA XIST suppresses nasopharyngeal carcinoma progression by activating miR‐491‐5p

“…Low expression of miR‐491‐5p has been reported in glioblastoma and oral squamous cell carcinoma . In NPC, we found that miR‐491‐5p was downregulated in NPC tissues compared with normal tissues and that miR‐491‐5p suppresses cell growth and invasion by targeting Notch3 . We therefore predicted that over‐expression of XIST was associated with dysregulation of Notch3 in NPC.…”

“…These results indicate that miR‐491‐5p suppresses XIST function. We previously reported that miR‐491‐5p suppresses Notch3 expression by directly targeting the 3′ untranslated region of Notch3 mRNA . Thus, XIST may regulate miR‐491‐5p to modulate Notch3 in NPC cells.…”

Up‐regulation of microRNA‐491‐5p suppresses cell proliferation and promotes apoptosis by targeting FOXP4 in human osteosarcoma

“…What's more, miR‐491 targets G‐protein‐coupled receptor kinase‐interacting protein 1 (GIT‐1), which blocked the activation of NF‐κB to attenuate cancer stem cell‐like properties of hepatocellular carcinoma . Besides, miR‐491 can also regulate its target genes, such as IGF2BP1, CTGF, TPX and Notch, functioning as tumour suppressor. Our study showed miR‐491‐5p suppressed the proliferation of human osteosarcoma cells and increased the cell apoptosis in vitro by targeting FOXP4 .…”

miR-491-5p, mediated by Foxi1, functions as a tumor suppressor by targeting Wnt3a/β-catenin signaling in the development of gastric cancer

“…4 Among these miRNAs, miR-491-5p, located in the fourth intron of focadhesin (FOCAD) has been reported to be deregulated in several human cancers. 5, 6, 7, 8, 9 miR-491-5p acts as a tumor suppressor by targeting JMJD2B in ERa-positive breast cancer. 10 miR-491-5p and its targeted gene GIT1 are considered biomarkers for the prognosis of oral squamous cell carcinoma.…”