Upregulation of Long Noncoding RNA SPRY4-IT1 Modulates Proliferation, Migration, Apoptosis, and Network Formation in Trophoblast Cells HTR-8SV/neo

Abstract

SPRY4-IT1 has been reported to have extremely high expression in normal placenta tissues. It is a Long noncoding RNA (lncRNA), which is associated with cell growth, migration, invasion, and apoptosis in melanoma. A 2.8-fold increase of SPRY4-IT1 expression was validated by Real-time reverse transcription-polymerase chain reaction (qRT-PCR) in severe preeclamptic placenta as compared with that of the normal ones (n=25) in this study. Furthermore, the role of SPRY4-IT1 in proliferation, migration, apoptosis, and network formation ability of trophoblast cells HTR-8/SVneo was assessed. Suppression of SPRY4-IT1 using siRNA treatment and its overexpression using plasmid targeting SPRY4-IT1 were performed in order to explore the biological function of SPRY4-IT1 in the development and progression of trophoblast cells HTR-8/SVneo, in vitro. The results showed that SPRY4-IT1 knockdown enhanced the cell migration and proliferation, and reduced the response of cells to apoptosis. However, exogenous SPRY4-IT1 overexpression significantly decreased the cell migration and proliferation, while increased cell apoptosis. Our study showed for the first time that aberrant expression of lncRNA SPRY4-IT1 might contribute to the abnormal condition of trophoblast cells HTR-8/SVneo. Therefore, we proposed SPRY4-IT1 as a novel lncRNA molecule, which might be associated with the pathogenesis of preeclampsia and might provide a new target for its early diagnosis and treatment.

Long non-coding RNA SPRY4-IT1 promotes the proliferation and invasion of U251 cells through upregulation of SKA2

“…Overexpression of SPRY4-IT1 has been shown to promote melanoma cell migration and invasiveness, whereas knockdown of SPRY4-IT1 inhibits melanoma cell invasion (17). The present study revealed that knockdown of SPRY4-IT1 inhibited the migration and invasion of U251 cells; however, this phenomenon was not consistent with the study reported by Zou et al conducted in trophoblast cells (27). Knockdown of SPRY4-IT1 induced the migration of HTR-8/SVneo cells, with overexpression of SPRY4-IT1 resulting in the inhibition of this migration (28).…”

The Lnc RNA SPRY4-IT1 Modulates Trophoblast Cell Invasion and Migration by Affecting the Epithelial-Mesenchymal Transition

“…In addition, Lan Xiao et al have shown that SPRY4-I1 is required for HuR binding to RNA; it also directly interacts with tight junction mRNAs and consequently regulates intestinal epithelial barrier function23 Moreover, in human placental tissues, SPRY4-IT1 exhibits differential expression in severe PE placenta, and it contributes to the biological activities of trophoblasts24. On the basis of these findings and according to the crucial influence of trophoblast migration and invasion, we further investigated the potential molecular mechanism by which SPRY4-IT1 regulates spiral artery remodelling in PE.…”

Long non-coding RNA SPRY4-IT1: a new player in different diseases

“…Zou et al found a higher expression level of SPRY4-IT1 in preeclampsic placental tissues as compared with the normal pregnancies [17] . In Trophoblast Cells (HTR-8/SVneo cells), the inhibition of SPRY4-IT1 led to the increase of migration rate and proliferation and the decrease of their apoptosis rate, while reverse results were observed in vitro when SPRY4-IT1 was overexpressed [17] .…”

“…In Trophoblast Cells (HTR-8/SVneo cells), the inhibition of SPRY4-IT1 led to the increase of migration rate and proliferation and the decrease of their apoptosis rate, while reverse results were observed in vitro when SPRY4-IT1 was overexpressed [17] . These phenomenon is contrary to most of malignant tumors above, indicating LncRNAs SPRY4-IT1 may show various phenotypes in different tissues and different stages of disease process.…”