Implication of the miR-184 and miR-204 Competitive RNA Network in Control of Mouse Secondary Cataract

Abstract

The high recurrence rate of secondary cataract (SC) is caused by the intrinsic differentiation activity of residual lens epithelial cells after extra-capsular lens removal. The objective of this study was to identify changes in the microRNA (miRNA) expression profile during mouse SC formation and to selectively manipulate miRNA expression for potential therapeutic intervention. To model SC, mouse cataract surgery was performed and temporal changes in the miRNA expression pattern were determined by microarray analysis. To study the potential SC counterregulative effect of miRNAs, a lens capsular bag in vitro model was used. Within the first 3 wks after cataract surgery, microarray analysis demonstrated SC-associated expression pattern changes of 55 miRNAs. Of the identified miRNAs, miR-184 and miR-204 were chosen for further investigations. Manipulation of miRNA expression by the miR-184 inhibitor (antimiR-184) and the precursor miRNA for miR-204 (pre-miR-204) attenuated SC-associated expansion and migration of lens epithelial cells and signs of epithelial to mesenchymal transition such as α-smooth muscle actin expression. In addition, pre-miR-204 attenuated SC-associated expression of the transcription factor Meis homeobox 2 (MEIS2). Examination of miRNA target binding sites for miR-184 and miR-204 revealed an extensive range of predicted target mRNA sequences that were also a target to a complex network of other SC-associated miRNAs with possible opposing functions. The identification of the SC-specific miRNA expression pattern together with the observed in vitro attenuation of SC by anti-miR-184 and pre-miR-204 suggest that miR-184 and miR-204 play a significant role in the control of SC formation in mice that is most likely regulated by a complex competitive RNA network.

Pax6 Regulates Gene Expression in the Vertebrate Lens through miR-204

“…EMT is characteristic of TGFβ-induced anterior subcapsular cataract formation, a pathology also associated with reduced dosage of Pax6 [44]–[46]. Interestingly, secondary cataract has recently been associated with alterations in miR-204 expression [47]. With this in mind, it is possible that part of Pax6 's activity in inhibiting cataract formation is mediated by the activity of miR-204 in the lens and that restoration of miR-204 levels may prevent anterior subcapsular cataract formation.…”

miR-204 Targeting of Ankrd13A Controls Both Mesenchymal Neural Crest and Lens Cell Migration

“…Interestingly, through in vitro studies, miR-204 has been associated with cell migration and invasiveness [15], [16], [17], [18], [19], [20]. However, it is completely unknown whether this miRNA has a similar function in cells of living organisms.…”

MicroRNA-204-5p-Mediated Regulation of SIRT1 Contributes to the Delay of Epithelial Cell Cycle Traversal in Diabetic Corneas

“…23 Recent studies by Zhang et al 24 found that miR-204 downregulates SIRT1 and reverts SIRT1-induced EMT in gastric cancer cells. During the process of EMT, they found that the expression of miR-204 was decreased, and upregulation of miR-204 reverted EMT by targeting SIRT1.…”