Knockdown of lncRNA LEF1-AS1 inhibited the progression of oral squamous cell carcinoma (OSCC) via Hippo signaling pathway

Abstract

It is verified that long non-coding RNAs (lncRNAs) play crucial roles in various cancers. LncRNA LEF1-AS1 is a reported oncogene in colorectal cancer and glioblastoma. In this study, we unveiled that LEF1-AS1 markedly increased in oral squamous cell carcinoma (OSCC) tissues and cell lines. Besides, OSCC patients with high levels of LEF1-AS1 were apt to poor prognosis. Functionally, LEF1-AS1 knockdown inhibited cell survival, proliferation and migration, whereas enhanced cell apoptosis and induced G0/G1 cell cycle arrest in vitro. Consistently, LEF1-AS1 silence hindered tumor growth in vivo. Moreover, LEF1-AS1 inhibition stimulated the activation of Hippo signaling pathway through directly interacting with LATS1. Furtherly, we disclosed that LEF1-AS1 silence abolished the interaction of LEF1-AS1 with LATS1 while enhanced the binding of LATS1 to MOB, therefore promoting YAP phosphorylation but impairing YAP1 nuclear translocation. Additionally, we demonstrated that LEF1-AS1 regulated YAP1 translocation via a LATS1-dependent manner. Furthermore, we also uncovered that YAP1 overexpression abolished the suppressive impact of LEF1-AS1 repression on the biological processes of OSCC cells. In a word, we concluded that LEF1-AS1 served an oncogenic part in OSCC through suppressing Hippo signaling pathway by interacting with LATS1, suggesting the therapeutic and prognostic potential of LEF1-AS1 in OSCC.

Long non‐coding RNA LEF1‐AS1 is involved in the progression of retinoblastoma through regulating the Wnt/β‐catenin pathway

“…Besides, LEF1‐AS1 expression was found to be associated with the depth of the invasion, lymph node metastasis, distant metastasis, and Ki67 index in patients with colorectal cancer . Zhang et al suggested that patients with oral squamous cell carcinoma in stage IV had notably elevated levels of LEF1‐AS1 expression in comparison to those in stages I–III. Overall, LEF1‐AS1 overexpression is associated with clinical progression in many types of human malignancies.…”

“…13 LEF1-AS1 has been suggested to play a role as a tumour-associated lncRNA in several types of human cancers, such as lung cancer, 14,15 esophageal squamous cell carcinoma, 16 breast, 17 colorectal, 18,19 and prostate cancers, 20 glioblastoma, 21 myeloid malignancy, 22 and oral squamous cell carcinoma. 23 Therefore, we hypothesized that LEF1-AS1 might also function as an oncogenic lncRNA in retinoblastoma. In our study, we found that LEF1-AS1 was overexpressed in retinoblastoma tissues and associated with the malignant status of patients suffering from the disease.…”

<p>LncRNA LEF1-AS1 Promotes Ovarian Cancer Development Through Interacting with miR-1285-3p</p>

“…26 LEF1-AS1 was also demonstrated to regulate proliferation and metastasis of oral squamous cell carcinoma and myeloid tumor. 16,27 Thus, LEF1-AS1 is a very important lncRNA involved in tumorigenesis. Nevertheless, whether LEF1-AS1 regulates ovarian cancer development remains uninvestigated.…”

“…Previously, lncRNA LEF1-AS1 was shown to promote progression of glioblastoma, prostate cancer, lung cancer and oral squamous cell carcinoma. [14][15][16][17] Nevertheless, whether LEF1-AS1 participates in ovarian cancer remains unknown.…”

Linc01234 promotes cell proliferation and metastasis in oral squamous cell carcinoma via miR-433/PAK4 axis

“…At present, numerous studies have confirmed that lncRNAs are involved in cell proliferation, apoptosis, migration and metabolism in OSCC [6]. For example, lncRNA LEF1-AS1 is remarkedly upregulated in OSCC tissues and servs as an oncogene in OSCC by suppressing the Hippo signaling pathway [7]. LncRNA MEG3 exerted an antitumor effect on cell growth and metastasis in OSCC by suppressing the activity of the WNT/β-catenin pathway [8].…”