Abstract
LIM domain only 3 (LMO3) interacts with transcription factors to regulate target genes involved in embryonic development. The oncogenic role of LMO3 in hepatocellular carcinoma, gastric cancer, and neuroblastoma has been reported recently. However, little is known about the biological function of LMO3 in papillary thyroid carcinoma (PTC). First, expression of LMO3 was dramatically enhanced in the PTC tissues and cell lines. Second, knockdown of LMO3 in PTC cells repressed cell proliferation and promoted cell apoptosis with downregulated Bcl-2 and upregulated cleaved caspase-3/PARP. In vitro cell migration and invasion of PTC were also retarded by siRNA-mediated silence of LMO3. Third, protein expression of LIM kinase (LIMK) 1-mediated phosphorylation of cofilin and nuclear translocation of β-catenin were reduced by the knockdown of LMO3. pcDNA-mediated overexpression of LIMK1 promoted cofilin phosphorylation and attenuated LMO3 silence-induced decrease of cofilin phosphorylation. Last, enhanced LIMK1 expression promoted PTC cell proliferation and metastasis and counteracted the suppressive effects of LMO3 silence on PTC cell proliferation and metastasis. In conclusion, LMO3 promoted PTC cell proliferation and metastasis by regulating LIMK1-mediated cofilin and the β-catenin pathway.
Highlights
Thyroid cancer, including papillary thyroid carcinoma (PTC), follicular thyroid cancer (FTC), medullary thyroid cancer (MTC), and anaplastic thyroid cancer (ATC), is the most common cancer of the endocrine system [1]
Protein expression of cleaved caspase-3 and cleaved PARP were enhanced, while Bcl-2 was reduced in TPC-1 and CAL62 that were transfected with siLMO3-1# and 2# (Figure 2e), suggesting the anti-proliferative and pro-apoptotic effects of LIM domain only 3 (LMO3) silence on PTC
Since LMO3 was found to be upregulated in the thyroid tumor [11], the biological function of LMO3 on PTC progression was investigated in this study
Summary
Thyroid cancer, including papillary thyroid carcinoma (PTC), follicular thyroid cancer (FTC), medullary thyroid cancer (MTC), and anaplastic thyroid cancer (ATC), is the most common cancer of the endocrine system [1]. The increased incidence and the stable mortality rate of thyroid cancer appear to be due to the devoid of effective therapeutic strategies [1]. LMO3 has been reported to regulate tumor signal transduction pathways through binding with other transcriptional factors. LMO3 is a key downstream target of transcription signal of and participates in the NK2 Homeobox 1-mediated occurrence of lung cancer [5]. Nescient helix-loop-helix 2 binds to LMO3 to downregulate the expression of hes family bHLH transcription factor 1 through transactivation of achaetescute complex-like 1 and induces malignant transformation of neuroblastoma [6]. LMO3 binds to the tumor suppressor gene p53 and inhibits the transcriptional activation of apoptotic proteins downstream of p53 [7]. Recent research has reported that the expression level of LMO3 was increased in thyroid tumor [11]. Little is known about the biological function of LMO3 in tumorigenicity of PTC
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