Long noncoding RNA HOTAIR mediates the estrogen-induced metastasis of endometrial cancer cells via the miR-646/NPM1 axis

Abstract

LncRNA homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) has been confirmed to be involved in the tumorigenic progression of endometrial carcinoma (EC). However, the molecular mechanisms of HOTAIR in EC are not fully elucidated. The expression of HOTAIR and miR-646 in human EC tissues was determined by qRT-PCR. The effect of miR-646 on EC cells was assessed by the cell viability, migration, and invasion using CCK-8 assays and transwell assays. RNA-binding protein immunoprecipitation assays and RNA pull-down assays were performed to explore the interaction between HOTAIR and miR-646. The regulation of miR-646 on nucleophosmin 1 (NPM1) was tested using luciferase reporter assays. MiR-646 expression was significantly decreased both in human EC tissues ( n = 23) and cell lines (Ishikawa and HEC-1-A) compared with the control. Moreover, miR-646 expression was negatively related to HOTAIR in human EC tissues ( n = 23). Our results also showed that miR-646 overexpression considerably attenuated the E2-promoted viability, migration, and invasion of Ishikawa and HEC-1-A cells in vitro. In addition, HOTAIR was confirmed to regulate the viability, migration, and invasion of EC cells through negative regulating miR-646. More importantly, we also demonstrated that NPM1 was the target of miR-646, and HOTAIR promoted NPM1 expression through interacting with miR-646 in EC cells. Taken together, our findings presented that HOTAIR could regulate NPM1 via interacting with miR-646, thereby governing the viability, migration, and invasion of EC cells.

RETRACTED: Long Noncoding RNA HOXB-AS1 Is Upregulated in Endometrial Carcinoma and Sponged miR-149-3p to Upregulate Wnt10b

“… 12 Many HOX genes, such as HOXB9, HOXB13, HOXA10, and HOTAIR, have demonstrated abnormal expression in EC tissues and cells. 13 - 16 HOXB cluster antisense RNA 1 (HOXB-AS1) has been demonstrated to facilitate the proliferation of glioblastoma cells and multiple myeloma cells. 17 , 18 However, a little is known about the functional role and molecular mechanism of HOXB-AS1 in EC.…”

Long Noncoding RNA HOTAIR Promotes Endometrial Carcinoma Cell Proliferation by Binding to PTEN via the Activating Phosphatidylinositol 3-Kinase/Akt Signaling Pathway

“…These findings implied that dysfunction of HOTAIR exerts crucial modulation on tumor cell proliferation, apoptosis, migration, and invasion through the regulation of various genes to participate in tumor progression and development (22). At present, there have been many studies showing that HOTAIR can participate in tumor progression, including in EC, through various pathways (23)(24)(25). In the present study, we found that HOTAIR was significantly upregulated in EC tissues compared with levels in control tissues.…”

Long non-coding RNA HOTAIR promotes osteoarthritis progression via miR-17-5p/FUT2/β-catenin axis

“…HOTAIR/miR-20a-5p/HMGA2 axis influenced cell growth, migration, invasion and apoptosis in breast cancer 33 . HOTAIR also regulated NPM1 via interacting with miR-646, thereby governing the viability, migration and invasion of endometrial cancer 34 . Our current research observed an inverse correlation between HOTAIR and miR-17-5p, which stimulated our interest to determine whether there was a ceRNA mechanism involved between HOTAIR and miR-17-5p.…”