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CircATP5C1 drives papillary thyroid carcinoma progression through HNRNPR nuclear export and BCL2L1 upregulation in a ubiquitination‑dependent manner

Listed in NCBI GEO

Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy, and aggressive PTC phenotypes contribute to poor patient prognosis.

Description

Circular RNAs (circRNAs) are stable non-coding RNAs critically involved in tumor progression, yet their regulatory mechanisms in PTC remain largely unclear. Here, we investigated the oncogenic role and molecular mechanism of circATP5C1 in PTC.

We conducted polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), RNA sequencing, RNA immunoprecipitation (RIP), co-immunoprecipitation (Co-IP), western blot, along with CCK-8, colony formation and wound-healing assays to explore circATP5C1 expression and function. A subcutaneous xenograft mouse model was further used for in vivo validation. CircATP5C1 was markedly upregulated in PTC tissues and closely correlated with extrathyroidal extension and lymph node metastasis.

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Functional assays confirmed that circATP5C1 promoted PTC cell proliferation and migration in vitro and facilitated tumor growth in vivo. Mechanistically, circATP5C1 directly binds heterogeneous nuclear ribonucleoprotein R (HNRNPR), enhances its ubiquitination and nuclear export. Cytoplasmic HNRNPR further stabilizes BCL2L1 mRNA and upregulates its expression.

Treatment with the ubiquitination inhibitor PYR-41 blocked HNRNPR nuclear export and reversed circATP5C1-mediated oncogenic effects. Collectively, circATP5C1 acts as an oncogenic circRNA to drive PTC progression via regulating HNRNPR-dependent BCL2L1 mRNA stability, providing a novel diagnostic biomarker and therapeutic target for PTC.

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Life Sciences
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Cancer 65% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE34382614 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 (65%)
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