Urothelial carcinoma associated 1 promotes trophoblast invasion by regulating MMP9

The long non-coding RNA UCA1 is reportedly increased in several human tumors and critical for the cell migration, invasion, or proliferation of several cancer cells. However, the potential roles of UCA1 in trophoblasts at early pregnancy still poorly understood. Here, we sought to unravel the roles of UCA1 in the occurrence of the recurrent miscarriage (RM) disorders.

The knockdown of UCA1 in human HTR-8 trophoblast cell line reduced their cell proliferative and invasive ability. Conversely, the UCA1 overexpression promoted the cell proliferation and invasion of HTR-8 cells. Quantitative RT-PCR screening revealed that UCA1 overexpression significantly enhanced MMP9, but not MMP2, mRNA expression in trophoblast cells. The overexpression of UCA1 also promoted trophoblast invasion by upregulating MMP9 expression and activity both in vitro and ex vivo. Consistently, UCA1 and MMP9 mRNA expression level was notably reduced in placental villi derived from patients with RM diseases.

This study revealed that UCA1 is critical for the regulation of invasive ability in trophoblasts. The abnormal UCA1/MMP9 pathway might result in the impaired trophoblast activities and lead to the development of RM. Our data may also provide a novel angle for the treatment in RM patients.