Dataset Information

Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis.

ABSTRACT:

Background

Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological function and molecular mechanism of lncRNA Fer-1 like family member 4 (FER1L4) in PTC.

Methods

The expression of FER1L4 in PTC was determined via operating quantitative real-time PCR assays. Meanwhile, the clinical significance of FER1L4 in patients with PTC was described. The biological functions of FER1L4 on PTC cells were evaluated by gain and loss of function experiments. Moreover, animal experiments were performed to reveal the effect on tumor growth. Subcellular distribution of FER1L4 was determined by fluorescence in situ hybridization and subcellular localization assays. Luciferase reporter assay and RNA immunoprecipitation assay were applied to define the relationship between FER1L4, miR-612, and Cadherin 4 (CDH4).

Results

Upregulated expression of FER1L4 in PTC tissues was positively correlated with lymph node metastasis (P = 0.020), extrathyroidal extension (P = 0.013) and advanced TNM stages (P = 0.013). In addition, knockdown of FER1L4 suppressed PTC cell proliferation, migration, and invasion, whereas ectopic expression of FER1L4 inversely promoted these processes. Mechanistically, FER1L4 could competitively bind with miR-612 to prevent the degradation of its target gene CDH4. This condition was further confirmed in the rescue assays.

Conclusions

This study first demonstrates FER1L4 plays an oncogenic role in PTC via a FER1L4-miR-612-CDH4 axis and may provide new therapeutic and diagnostic targets for PTC.

SUBMITTER: Wu L

PROVIDER: S-EPMC8296567 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Our previous study introduced the oncogenic role of the long non-coding RNA plasmacytoma variant translocation 1 (PVT1) in endometrial cancer (EC). In this study, we aimed to construct a PVT1-centered competing endogenous RNA (ceRNA) network to outline a regulatory axis that might promote the malignant progression of advanced EC. Raw Uterine Corpus Endometrial Carcinoma (UCEC) datasets were collected from The Cancer Genome Atlas (TCGA) database and used for construction of the PVT1-centered ceRNA network. The ceRNA binding sites were established using dual-luciferase assays. FISH assays displayed the co-location of PVT1 and miR-612 in EC cells. Immunohistochemistry, in situ hybridization, qRT-PCR, and western blots were used to assess the expression of miR-612 and CENP-H in EC tissues, and their functions on biological behaviours were examined by a series of in vitro and in vivo assays. Molecule interactions were illustrated by co-transfection assays. The bioinformatics analysis showed that PVT1/miR-612/CENP-H/CDK1 axis played a vital role in the malignant progression of advanced EC. MiR-612 was downregulated in EC tissues and acted as a tumour suppressor to inhibit cell proliferation, migration, invasion, and promote cell apoptosis. CENP-H was found overexpressed in EC tissues, and the expression level was correlated to diagnosis and prognosis of EC. Hyperactivated CENP-H promoted cell proliferation, migration, invasion, and inhibited cell apoptosis. Overexpressed CENP-H prevented the anti-tumour effects observed with upregulated miR-612; knockdown of miR-612 also suppressed the anti-tumour effects of downregulated PVT1. Knockdown of PVT1 together with upregulated miR-612 exerted the strongest anti-tumour effects in nude mice. These effects were mediated by CDK1 through modulation of the Akt/mTOR signaling pathway. In conclusion, the PVT1/miR-612/CENP-H/CDK1 axis promoted the malignant progression of advanced EC and could serve as a promising target for potential treatments.