Knockdown of TACC3 inhibits trophoblast cell migration and invasion through the PI3K/Akt signaling pathway

Abstract

The insufficient invasion of trophoblasts is known to be correlated with the development of preeclampsia. Transforming acidic coiled‑coil protein 3 (TACC3), a member of the TACC domain family, is important in the regulation of cell differentiation, migration and invasion. However, the role of TACC3 in trophoblast function during placental development remains to be fully elucidated. The present study aimed to determine the expression and function of TACC3 in human placenta and to examine the underlying mechanisms. TACC3 expression was analyzed in preeclamptic placentas using reverse transcription‑quantitative polymerase chain reaction and western blotting. Cell proliferation was determined by the MTT assay, and cell migration and invasion were measured using Transwell assays. The expression levels of TACC3, matrix metalloproteinase (MMP)‑2, MMP‑9, tissue inhibitor of metalloproteinase (TIMP)‑1, TIMP‑2, phosphoinositide 3‑kinase (PI3K), phosphorylated (p)‑PI3K, AKT and p‑AKT were detected by western blotting. The results showed that the expression of TACC3 was downregulated in preeclamptic placentas. The knockdown of TACC3 significantly inhibited HTR8/SVneo cell proliferation, migration and invasion, and inhibited the expression of matrix metalloproteinases. In addition, the knockdown of TACC3 significantly reduced the levels of p‑PI3K and Akt in the HTR8/SVneo cells. Taken together, the results of the present study demonstrated that the knockdown of TACC3 inhibited the migration and invasion of HTR8/SVneo cells through suppression of the PI3K/Akt signaling pathway. Therefore, TACC3 may serve as a novel potential target for treating preeclampsia.

ANXA4 promotes trophoblast invasion via the PI3K/Akt/eNOS pathway in preeclampsia

“…4A). Furthermore, MMP-2 and MMP-9 have been shown to be critical in trophoblast invasion by degrading the extracellular matrix (30). Our results showed that ANXA4 overexpression significantly increased the protein expression of MMP-2 and MMP-9 in HTR-8/SVneo cells (Fig.…”

“…The PI3K/Akt signaling pathway plays a critical role in mediating the growth-factor-dependent regulation of trophoblast growth and invasion. A previous study has stated that migration and invasion of trophoblast cells are suppressed through inhibition of the PI3K/Akt pathway (30). PI3K and Akt are involved in regulating trophoblast invasion through the upregulation of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression by epidermal growth factor (18).…”

“…Furthermore, placentas from PE patients exhibited reduced levels of endothelial nitric oxide synthase (eNOS) expression (3,5,12). It has been reported that activation of PI3K/Akt/eNOS pathways plays an important role in regulating cell migration, angiogenesis, and preventing hypertension (7,29,30).…”

The role of TACC3 in mitotic spindle organization

“…TACC3 is highly expressed in most cancers tissues, such as prostate cancer (Li et al, ), glioma (Sun et al, ), cholangiocarcinoma (He et al, ), and colorectal cancer (Du et al, ), lung cancer (Jiang et al, ), gastric cancer (Yun et al, ). However, the expression of TACC3 is down‐regulated in thyroid cancer and ovarian carcinoma and preeclampsia (Peters et al, ; Ulisse et al, ; Zhu, Cao, Li, & Wang, ). Extensive and abnormal expression patterns of TACC3 in cancers make it more attractive than the other two proteins.…”

Silencing BRIT1 Facilitates the Abilities of Invasiveness and Migration in Trophoblast Cells

“…Among members of the MMP family, MMP-2 and MMP-9 are the most studied and play the most important roles in trophoblast cell invasion [39–41]. Its inhibitory factor, TIMPs, inhibits invasion [42,43]. To test our hypothesis, we studied the impact of si-BRIT1 on the activities of MMP-2, MMP-9, TIMP-1, and TIMP-2 in TC.…”