title: miR-30a suppresses cell migration and invasion through downregulation of PIK3CD in colorectal carcinoma.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) play key roles in tumor metastasis. The aim of this study was to determine the regulation and function of miR-30a in colorectal carcinoma (CRC) metastasis.
  
  
  METHODS
  The expression of miR-30a was detected in CRC cell lines and samples by qRT-PCR. The anti-metastatic effect of miR-30a was determined by both in vitro and in vivo assays. A luciferase reporter assay was performed to determine target association between miR-30a and phosphoinositide 3-kinase catalytic subunit delta (PIK3CD).
  
  
  RESULTS
  miR-30a was significantly downregulated in highly metastatic CRC cell lines and metastatic tissues. Overexpression of miR-30a suppressed CRC cell migration and invasion in vitro and liver metastasis in vivo, whereas miR-30a deletion dramatically promoted cell migration and invasion. Further studies revealed that PIK3CD is a direct target of miR-30a as miR-30a bounds directly to the 3'-UTR of PIK3CD, subsequently reducing its expression. Similar to the restoring miR-30a expression, PIK3CD downregulation inhibited cell migration and invasion, whereas PIK3CD overexpression rescued the suppressive effect of miR-30a. Moreover, significant downregulation of miR-30a in metastatic CRC tissues was found to be inversely correlated with PIK3CD expression. Mechanistic studies revealed that miR-30a down-regulated the expression of key components of the Akt/mTOR pathway, whereas PIK3CD overexpression reversed this negative effect.
  
  
  CONCLUSIONS
  Our findings indicate that miR-30a might function as a metastasis suppressor in CRC. miR-30a may be a potential therapeutic target to block CRC metastasis.
authors.affiliation: Department of General Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
authors.forename: Zhengqian
authors.initials: Z
authors.lastname: Bian
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D006801:Humans; D008207:Lymphatic Metastasis / Q000517:prevention & control; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D020413:3' Untranslated Regions; D058534:Class I Phosphatidylinositol 3-Kinases; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546086:MIRN30b microRNA, human; C486018:PIK3CD protein, human