Possible role of HIWI2 in modulating tight junction proteins in retinal pigment epithelial cells through Akt signaling pathway

Abstract

PIWI subfamily of proteins is shown to be primarily expressed in germline cells. They maintain the genomic integrity by silencing the transposable elements. Although the role of PIWI proteins in germ cells has been documented, their presence and function in somatic cells remains unclear. Intriguingly, we detected all four members of PIWI-like proteins in human ocular tissues and somatic cell lines. When HIWI2 was knocked down in retinal pigment epithelial cells, the typical honeycomb morphology was affected. Further analysis showed that the expression of tight junction (TJ) proteins, CLDN1, and TJP1 were altered in HIWI2 knockdown. Moreover, confocal imaging revealed disrupted TJP1 assembly at the TJ. Previous studies report the role of GSK3β in regulating TJ proteins. Accordingly, phospho-kinase proteome profiler array indicated increased phosphorylation of Akt and GSK3α/β in HIWI2 knockdown, suggesting that HIWI2 might affect TJ proteins through Akt-GSK3α/β signaling axis. Moreover, treating the HIWI2 knockdown cells with wortmannin increased the levels of TJP1 and CLDN1. Taken together, our study demonstrates the presence of PIWI-like proteins in somatic cells and the possible role of HIWI2 in preserving the functional integrity of epithelial cells probably by modulating the phosphorylation status of Akt.

PIWI-like protein, HIWI2 is aberrantly expressed in retinoblastoma cells and affects cell-cycle potentially through OTX2

“…Though increased expression of HIWI2 is reported in cervical cancer tissues, Y79 showed higher expression of HIWI2 than the levels reported in cervical cancer cells [19]. This could be attributed to the cellular origin of cancer, which correlates with the finding from our previous study showing higher expression of PIWI-like proteins in the retina than in the retinal pigment epithelium (RPE) [11]. …”

“…In our previous report, we demonstrated the effects of HIWI2 silencing on the Akt pathway [11]. OTX2 is known to be activated by the PI3K/Akt signalling axis [32].…”

“…We recently demonstrated the function of HIWI2 in somatic cells, where it plays a role in maintaining the integrity of retinal pigment epithelial cells by regulating the Akt/GSK3 pathway [11]. Other recent reports have shown the abnormal expression of PIWI-like proteins in various cancers, where they are known to promote cell division, resist apoptosis and facilitate cell invasion and migration [12].…”

Landscape of microRNA in the aqueous humour of proliferative diabetic retinopathy as assessed by next‐generation sequencing

“…piRNAs, a class of small non‐coding RNAs associated with piwi, maintain genomic integrity through transposon silencing . Most piRNA studies focus on germline and stem cells; however, a couple of studies have found that piRNAs were also expressed in somatic tissues such as liver, heart, brain and retina tissues . Piwi proteins and their associated piRNAs were demonstrated to control the beta cell functions and be involved in the development of type 2 diabetes .…”

“…45 Most piRNA studies focus on germline and stem cells; however, a couple of studies have found that piRNAs were also expressed in somatic tissues such as liver, heart, brain and retina tissues. 46,47 Piwi proteins and their associated piRNAs were demonstrated to control the beta cell functions and be involved in the development of type 2 diabetes. 48 One study identified miRNA, piRNA and other sRNAs in the eyes of adult newts and found that these sRNAs may be involved in the regeneration of a newt's lens and retina.…”