PubMed:23469214
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/23469214","sourcedb":"PubMed","sourceid":"23469214","source_url":"https://www.ncbi.nlm.nih.gov/pubmed/23469214","text":"Feedback regulations of miR-21 and MAPKs via Pdcd4 and Spry1 are involved in arsenite-induced cell malignant transformation.\nOBJECTIVE: To establish the functions of miR-21 and the roles of two feedback regulation loops, miR-21-Spry1-ERK/NF-κB and miR-21-Pdcd4-JNK/c-Jun, in arsenite-transformed human embryo lung fibroblast (HELF) cells.\nMETHODS: For arsenite-transformed HELF cells, apoptosis, clonogenicity, and capacity for migration were determined by Hoechst staining, assessment of their capacity for anchorage-independent growth, and wound-healing, respectively, after blockage, with inhibitors or with siRNAs, of signal pathways for JNK/c-Jun or ERK/NF-κB. Decreases of miR-21 levels were determined with anti-miR-21, and the up-regulation of Pdcd4 and Spry1 was assessed in transfected cells; these cells were molecularly characterized by RT-PCR, qRT-PCR, Western blots, and immunofluorescence assays.\nRESULTS: MiR-21 was highly expressed in arsenite-transformed HELF cells and normal HELF cells acutely treated with arsenite, an effect that was concomitant with activation of JNK/c-Jun and ERK/NF-κB and down-regulation of Pdcd4 and Spry1 protein levels. However, there were no significant changes in mRNA levels for Pdcd4 and Spry1, which suggested that miR-21 regulates the expressions of Pdcd4 and Spry1 through translational repression. In arsenite-transformed HELF cells, blockages of JNK/c-Jun or ERK/NF-κB with inhibitors or with siRNAs prevented the increases of miR-21and the decreases of the protein levels but not the mRNA levels of Pdcd4 and Spry1. Down-regulation of miR-21 and up-regulations of Pdcd44 or Spry1 blocked the arsenite-induced activations of JNK/c-Jun or ERK/NF-κB, indicating that knockdown of miR-21 inhibits feedback of ERK activation and JNK activation via increases of Pdcd4 and Spry1 protein levels, respectively. Moreover, in arsenite-transformed HELF cells, inhibition of miR-21 promoted cell apoptosis, inhibited clonogenicity, and reduced migration.\nCONCLUSION: The results indicate that miR-21 is both a target and a regulator of ERK/NF-κB and JNK/c-Jun and the feedback regulations of miR-21 and MAPKs via Pdcd4 and Spry1, respectively, are involved in arsenite-induced malignant transformation of HELF cells.","tracks":[{"project":"Allie","denotations":[{"id":"SS1_23469214_2_0","span":{"begin":296,"end":324},"obj":"expanded"},{"id":"SS2_23469214_2_0","span":{"begin":326,"end":330},"obj":"abbr"}],"relations":[{"id":"AE1_23469214_2_0","pred":"abbreviatedTo","subj":"SS1_23469214_2_0","obj":"SS2_23469214_2_0"}],"attributes":[{"subj":"SS1_23469214_2_0","pred":"source","obj":"Allie"},{"subj":"SS2_23469214_2_0","pred":"source","obj":"Allie"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Allie","color":"#a2ec93","default":true}]}]}}