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.

A key regulatory loop AK4P1/miR-375/SP1 in pancreatic adenocarcinoma

“…Some of these pseudogene-derived RNAs have been reported to be involved in the development and progression of human cancers. For instance, FER1L4 played critical roles in multiple malignancies, including papillary thyroid cancer [ 11 ], colorectal cancer [ 12 ], liver cancer [ 13 ], oral squamous cell carcinoma [ 14 ]. Next, stage expression analysis for the 20 RNAs was conducted in pancreatic adenocarcinoma by GEPIA database, and three RNAs (RP11-719K4.3, FER1L4 and AK4P1) were selected for subsequent study.…”

Cytosolic Cadherin 4 promotes angiogenesis and metastasis in papillary thyroid cancer by suppressing the ubiquitination/degradation of β-catenin

“…The HA-Ub plasmid (pCMV-HA-Ub), His-CDH4 plasmid (pCMV-6 × His-CDH4), and Flag-β-catenin plasmid (pCDEF-FLAG-β-catenin) were obtained from Miaoling (Wuhan, China). Transfection techniques adhered to previously reported methods and manufacturer's instructions [ 18 ]. The specific sequences of the siRNA or shRNA mentioned above can be found in Additional file 1 : Table S1.…”

“…In terms of invasion assays, cells were seeded on Matrigel-coated upper chambers. The detailed protocol has been described previously [ 18 ].…”

“…This observation underscores the intricate regulation and context-dependent nature of cadherins in different malignancies. Although we previously demonstrated that CDH4 could promote PTC cell proliferation and invasion while being regulated by long noncoding RNA FER1L4, the role of CDH4 in PTC progression and metastasis is still unclear [ 18 ].…”

Mesenchymal Stem Cell-Derived from Dental Tissues-Related lncRNAs: A New Regulator in Osteogenic Differentiation

“…In various tumors, it plays a role in the occurrence and development, and cells in cancer can be inhibited from proliferating and migrating, such as esophageal squamous cells, carcinoma cells [98], hepatocellular carcinoma cells [99], and endometrial cancer cells [100]. But can promote the invasion and targeting of papillary thyroid cancer [101] and the progression of oral squamous cell carcinoma [102]. lncRNA FER1L4 has a little study on bone diseases, but some scholars have found that it can be a positive regulator of osteogenic diferentiation in PDLSCs by targeting miR-874-3p/VEGFA.…”