Tumor-suppressing effects of microRNA-612 in bladder cancer cells by targeting malic enzyme 1 expression

The present study investigated the possible tumor-suppressing function of microRNA (miR)-612 and the underlying molecular mechanism of its action in bladder cancer in vitro and in vivo. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was carried out to quantify the expression levels of miR-612 in bladder cancer tissues and cell lines. The data demonstrated that the level of miR-612 expression was significantly reduced in bladder cancer tissues and cell lines, as compared with that in non-cancerous tissues and cells. Reduced miR-612 expression was associated with advanced tumor, lymph node and metastasis stages, and with distant metastasis of bladder cancer. A functional study revealed that transfection of cells with an miR-612 mimic suppressed bladder cancer cell growth, colony formation, migration, invasion and epithelial-mesenchymal transition. Bioinformatics analysis identified that miR-612 targeted the expression of malic enzyme 1 (ME1), and this was confirmed by western blot and luciferase reporter assay results. Furthermore, the ME1 expression levels were inversely associated with miR-612 expression in bladder cancer tissue specimens. In addition, knockdown of ME1 expression using ME1 siRNA mimicked the effect of ectopic miR-612 overexpression in bladder cancer cells in terms of tumor cell growth, migration and invasion. By contrast, ME1 overexpression weakened the inhibitory effect of the miR-612 mimic in bladder cancer cells. In conclusion, the present study demonstrated that miR-612 may function as a tumor suppressor in bladder cancer by targeting ME1 expression.

• Publication year

  2018

• Venue

  International Journal of Oncology

• Publication date

  2018-03-29

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3892/ijo.2018.4342PMID 29620192PMCID 5919718
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• ME1 knockdown phenocopies ectopic miR-612 overexpression, whereas ME1 overexpression weakens the inhibitory effect of the miR-612 mimic in bladder cancer cells.

  Confidence 0.93

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• microRNA-612 directly targets malic enzyme 1 expression, supported by luciferase reporter and western blot results.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• miR-612 mimic transfection suppresses bladder cancer cell growth, colony formation, migration, invasion, and epithelial-mesenchymal transition.

  Confidence 0.96

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• microRNA-612 expression is reduced in bladder cancer tissues and cell lines, and lower expression is associated with advanced stage and metastasis.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review

• bladder cancer

  cancer type, disease

  The malignant disease context studied using patient tissue specimens and bladder cancer cell lines.

  Aliases: BC

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• epithelial-mesenchymal transition

  cellular process

  A cell-state program associated with changes in epithelial and mesenchymal markers and motility in cancer cells.

  Aliases: EMT

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• malic enzyme 1

  gene, protein

  An enzyme-encoding gene and protein examined as a predicted target of miR-612 in bladder cancer cells.

  Aliases: ME1

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• me1 sirna

  RNA interference reagent, molecular reagent

  A small interfering RNA reagent used to reduce ME1 expression in bladder cancer cells.

  Aliases: siME1

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• microrna-612

  microRNA

  A microRNA investigated in bladder cancer tissues and cell lines as a regulator of tumor-related behavior.

  Aliases: miR-612

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review
• mir-612 mimic

  molecular reagent, RNA mimic

  A synthetic RNA reagent used to increase cellular miR-612 activity in transfected bladder cancer cells.

  Aliases: miR-612 mimic transfection

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewjaeyoung (rb9u4m834j) review

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