| General information | Literature | Expression | Regulation | Mutation | Interaction |
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Basic Information |
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Gene ID | 5602 |
Name | MAPK10 |
Synonymous | JNK3|JNK3A|PRKM10|SAPK1b|p493F12|p54bSAPK;mitogen-activated protein kinase 10;MAPK10;mitogen-activated protein kinase 10 |
Definition | JNK3 alpha protein kinase|MAP kinase 10|MAP kinase p49 3F12|MAPK 10|c-Jun N-terminal kinase 3|stress activated protein kinase beta|stress-activated protein kinase 1b|stress-activated protein kinase JNK3 |
Position | 4q22.1-q23 |
Gene type | protein-coding |
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Title |
Abstract |
| Identification of MAPK10 as a novel epigenetic marker for chromophobe kidney cancer. | CONTEXT: Loss of the thyroid hormone receptor is common in tumors. In mouse models, a truncated THRB gene leads to thyroid cancer. Previously, we observed up-regulation of the expression of eight microRNAs (miRs) in papillary thyroid carcinoma (PTC) tumors. OBJECTIVE: Our objective was to determine whether THRB might be inhibited by miRs up-regulated in PTC. DESIGN: The potential binding of miR to the 3-untranslated region of THRB was analyzed in silico. Direct inhibition by miRs binding to the cloned 3-untranslated region of THRB was evaluated using luciferase assays. Inhibition of endogenous THRB and its target genes (DIO1 and APP) was examined in cell lines transfected by pre-miRs. The impact on thyroid hormone response element (TRE) was evaluated in promoter assays. Correlations between the expression of THRB and miRs was evaluated in 13 PTC tumor/normal tissue pairs. RESULTS: THRB contains binding sites for the top seven miRs up-regulated in PTC (P = 0.0000002). Direct interaction with THRB was shown for miR-21 and miR-146a. We observed lower levels of THRB transcripts in cell lines transfected with miR-21, -146a, and -221 (down-regulation of 37-48%; P < 0.0001), but not with miR-181a. THRB protein was suppressed down to 10-28% by each of four miRs. Concomitant expression of DIO1 and APP was affected (down-regulation of 32-66%, P < 0.0034 and up-regulation of 48-57%, P < 0.0002, respectively). All four miRs affected TRE activity in promoter assays. Down-regulation of luciferase occurred after transfection with pTRE-TK-Luc construct and each of four miRs. The analysis of tumor/normal tissue pairs revealed down-regulation of THRB in 11 of 13 pairs (1.3- to 9.1-fold), and up-regulation of miR-21, -146a, -181a, and -221 in almost all pairs. CONCLUSIONS: MiRs up-regulated in PTC tumors directly inhibit the expression of THRB, an important tumor suppressor gene. |