RESUMEN
ObjectiveslncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) acts as an oncogene involved in papillary thyroid carcinoma (PTC) occurrence and progression. ABHD11-AS1 exerts biologic functions by some miRNAs and proteins to regulate multiple targets. Identification of novel mechanism of ABHD11‐AS1 could be helpful in therapeutic targeting for PTC treatment.MethodsDifferentially expressed lncRNAs were selected from TCGA database. qRT‐PCR analysis was applied to examine the expression of ABHD11‐AS1 in PTC cell lines and tissues. The relationship of ABHD11-AS1 expression and clinicopathological features was analyzed by KaplanMeier analysis.Two PTC cell lines (TPC-1 and KTC-1) were transfected with pcDNA 3.1, pcDNA3.1-ABHD11-AS1, si-NC and si-ABHD11-AS1, respectively, to verify the ABHD11-AS1 oncogene-regulating capacity to promote tumor progression. The cell metastasis and proliferation had been evaluated both in vitro and in vivo.ResultsHigh expression of ABHD11‐AS1 was found in PTC tissues (P < 0.01), which was significantly correlated with lymph node metastasis (P < 0.05). ABHD11-AS1 overexpression noticeably promoted cell proliferation, migration, and invasion capabilities, which were obviously decreased upon ABHD11-AS1 knockdown. ABHD11-AS1 positively regulated EGFR/EPS15L1 pathway, as EGFR, EPS15L1, STAT3, and p-STAT3 were activated.ConclusionABHD11‐AS1 promotes tumor progression in PTC by regulating EPS15L1/EGFR pathway.
Asunto(s)
Humanos , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , ARN sin Sentido/genética , Serina Proteasas/genética , Serina Proteasas/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVES: lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) acts as an oncogene involved in papillary thyroid carcinoma (PTC) occurrence and progression. ABHD11-AS1 exerts biologic functions by some miRNAs and proteins to regulate multiple targets. Identification of novel mechanism of ABHD11-AS1 could be helpful in therapeutic targeting for PTC treatment. METHODS: Differentially expressed lncRNAs were selected from TCGA database. qRT-PCR analysis was applied to examine the expression of ABHD11-AS1 in PTC cell lines and tissues. The relationship of ABHD11-AS1 expression and clinicopathological features was analyzed by Kaplan-Meier analysis. Two PTC cell lines (TPC-1 and KTC-1) were transfected with pcDNA 3.1, pcDNA3.1-ABHD11-AS1, si-NC and si-ABHD11-AS1, respectively, to verify the ABHD11-AS1 oncogene-regulating capacity to promote tumor progression. The cell metastasis and proliferation had been evaluated both in vitro and in vivo. RESULTS: High expression of ABHD11-AS1 was found in PTC tissues (P < 0.01), which was significantly correlated with lymph node metastasis (P < 0.05). ABHD11-AS1 overexpression noticeably promoted cell proliferation, migration, and invasion capabilities, which were obviously decreased upon ABHD11-AS1 knockdown. ABHD11-AS1 positively regulated EGFR/EPS15L1 pathway, as EGFR, EPS15L1, STAT3, and p-STAT3 were activated. CONCLUSION: ABHD11-AS1 promotes tumor progression in PTC by regulating EPS15L1/EGFR pathway.
Asunto(s)
MicroARNs , ARN Largo no Codificante , Neoplasias de la Tiroides , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , ARN sin Sentido/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Serina Proteasas/genética , Serina Proteasas/metabolismo , Transducción de Señal/genética , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/patologíaRESUMEN
Split-hand/split-foot malformation (SHFM) is a severe form of congenital limb deformity characterized by the absence of 1 or more digits and/or variable degree of median clefts of hands and feet. The present study describes an investigation of a consanguineous family of Pakistani origin segregating SHFM in an autosomal recessive manner. Human genome scan using SNP markers followed by whole exome sequencing revealed a frameshift deletion (c.409delA, p.Ser137Alafs*19) in the EPS15L1 gene located on chromosome 19p13.11. This is the first biallelic variant identified in the EPS15L1 gene underlying SHFM. Our findings report the first direct involvement of EPS15L1 gene in the development of human limbs.