RGD Reference Report - MicroRNA-323-3p inhibits cell invasion and metastasis in pancreatic ductal adenocarcinoma via direct suppression of SMAD2 and SMAD3. - Rat Genome Database

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MicroRNA-323-3p inhibits cell invasion and metastasis in pancreatic ductal adenocarcinoma via direct suppression of SMAD2 and SMAD3.

Authors: Wang, Chunyou  Liu, Pian  Wu, Heshui  Cui, Pengfei  Li, Yongfeng  Liu, Yao  Liu, Zhiqiang  Gou, Shanmiao 
Citation: Wang C, etal., Oncotarget. 2016 Mar 22;7(12):14912-24. doi: 10.18632/oncotarget.7482.
RGD ID: 14394493
Pubmed: PMID:26908446   (View Abstract at PubMed)
PMCID: PMC4924761   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.7482   (Journal Full-text)

Pancreatic ductal adenocarcinoma (PDAC), which accounts for 96% of all pancreatic cancer cases, is characterized by rapid progression, invasion and metastasis. Transforming growth factor-beta (TGF-β) signaling is an essential pathway in metastatic progression and microRNAs (miRNA) play central roles in the regulation of various biological and pathologic processes including cancer metastasis. However, the molecular mechanisms involved in regulation of miRNAs and activation of TGF-β signaling in PDAC remain to be established. The results of this study suggested that miR-323-3p expression in PDAC tissues and cell lines was significantly decreased compared to levels in normal pancreatic tissues and primary cultured pancreatic duct epithelial cells. Further investigation revealed that miR-323-3p directly targeted and suppressed SMAD2 and SMAD3, both key components in TGF-β signaling. Lower levels of miR-323-3p predicted poorer prognosis in patients with PDAC. Ectopic overexpression of miR-323-3p significantly inhibited, while silencing of miR-323-3p increased the migration and invasion abilities of PDAC cells in vitro. Moreover, using an in vivo mouse model, we demonstrated that overexpressing of miR-323-3p significantly reduced, while knockdown of miR-323-3p enhanced lung metastatic colonization of PANC-1 cells. Furthermore, miR-323-3p-induced TGF-b signaling inhibition and cell motility suppression were partially rescued by overexpressing of Smad2 and Smad3 in PDAC cells. Our findings suggest that re-expression of miR-323-3p might offer a novel therapeutic target against metastasis in patients with PDAC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pancreatic ductal adenocarcinoma severityIEP 14394493 RGD 
pancreatic ductal adenocarcinoma severityISOSMAD2 (Homo sapiens)14394493; 14394493 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Smad2  (SMAD family member 2)

Genes (Mus musculus)
Smad2  (SMAD family member 2)

Genes (Homo sapiens)
SMAD2  (SMAD family member 2)


Additional Information