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Omics · study · 2026

POLR1F promotes proliferation and stemness of anaplastic thyroid cancer by activating F2R/p38 MAPK signaling

Listed in NCBI GEO

Anaplastic thyroid cancer (ATC) is one of the most aggressive cancers characterized with extremely rapid growth rate.

Description

Dysregulation of RNA polymerase (Pol) is critical for cancer development, but little is known about its role and mechanism in ATC. In the present study, the expressions of Pol family members were screened in a large-cohort proteome, which contained 113 ATCs and 20 normal thyroid samples.

Combined with gene dependency score, we found RNA Polymerase I Subunit F (POLR1F) was significantly upregulated in ATC tissues with the strongest gene effect among the Pol family members. The results were confirmed in ATC tissues and cell lines, revealing that POLR1F was mainly located in nuclei and expressed stronger than normal thyrocytes. Silence of POLR1F in ATC cell lines significantly inhibited cell proliferation, colony formation, and sphere sizes.

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POLR1F knockdown dramatically reduced tumor growth of ATC xenografts both in zebrafish and nude mice. RNA sequencing analysis revealed that coagulation factor thrombin receptor (F2R) was a downstream target of POLR1F participating in p38 MAPK pathway. Silence of F2R significantly inhibited ATC cell proliferation, colony number, and the ability of sphere formation.

F2R positively correlated with POLR1F and p38 MAPK signaling score. Both POLR1F and F2R knockdown evidently attenuated phosphorylation of p38 MAPK. Consistently, phosphorylation of p38 MAPK was reduced in ATC xenografts after POLR1F inhibition.

These results demonstrate POLR1F was required for ATC growth and stemness by activating F2R/p38 MAPK signaling, shedding light on an essential role of POLR1F in maintaining ATC aggressiveness.

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Life Sciences
Inferred from text
Cancer 75% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE29105413 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title