{"gene":"CCNL2","run_date":"2026-06-09T22:57:17","timeline":{"discoveries":[{"year":2016,"finding":"CCNL2 is a direct target of miR-214 in pulmonary artery smooth muscle cells (PASMCs); miR-214 binds to CCNL2 mRNA and suppresses its expression, promoting PASMC proliferation by suppressing apoptosis. Hypoxia increases miR-214 and decreases CCNL2, while miR-214 inhibitors reverse this, upregulating CCNL2 and attenuating proliferation.","method":"Luciferase reporter assay (target validation), RT-PCR, western blot, miR-214 mimic/inhibitor transfection, cell proliferation and apoptosis assays","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase assay plus functional rescue in a single lab with two orthogonal methods (reporter + cellular phenotype)","pmids":["27381447"],"is_preprint":false},{"year":2021,"finding":"KLF3 transcriptionally activates CCNL2 expression; miR-23a-3p (carried in osteoblast exosomes) targets KLF3, thereby suppressing KLF3-driven CCNL2 transcription and alleviating spinal cord ischemia/reperfusion injury. Rescue experiments confirmed the miR-23a-3p → KLF3 → CCNL2 regulatory axis.","method":"Co-culture experiments, GEO database mining, exosome treatment of SCIRI cells, luciferase/binding assays, rescue/overexpression experiments, RT-PCR and western blot","journal":"Developmental neuroscience","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, functional rescue experiments described but mechanistic detail on KLF3–CCNL2 transcriptional interaction is limited in the abstract","pmids":["34937039"],"is_preprint":false},{"year":2023,"finding":"lnc-RNU12 physically interacts with cyclin L2 (CCNL2) protein (and c-JUN) in Jurkat T cells, as verified by RNA-binding protein immunoprecipitation (RIP). Knockdown of lnc-RNU12 alters CCNL2 mRNA and protein expression and causes cell cycle S-phase arrest, placing CCNL2 downstream of lnc-RNU12 in T-cell cycle regulation.","method":"RNA-binding protein immunoprecipitation (RIP) assay, lncRNA knockdown in Jurkat T cells, cell cycle analysis, RT-PCR, western blot","journal":"Rheumatology (Oxford, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP assay plus functional knockdown with defined cell-cycle phenotype, single lab, two orthogonal methods","pmids":["36165706"],"is_preprint":false},{"year":2025,"finding":"YBX1 directly binds CCNL2 mRNA and stabilizes it via 5-methylcytosine (m5C) modification; mutation of the m5C-reader residue in YBX1 reduces CCNL2 expression. MATR3 interacts with YBX1 and cooperatively regulates CCNL2 levels; MATR3 knockdown reverses YBX1-induced CCNL2 upregulation. CCNL2 promotes ovarian cancer cell proliferation and cisplatin resistance.","method":"MeRIP assay (m5C detection), YBX1 mutagenesis, Co-IP (YBX1–MATR3 interaction), siRNA knockdown, xenograft and PDX models, in vitro proliferation and cisplatin sensitivity assays","journal":"Journal of ovarian research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — MeRIP assay, mutagenesis, and Co-IP in a single lab with multiple orthogonal methods","pmids":["40707993"],"is_preprint":false},{"year":2025,"finding":"CCNL2 is an activating cyclin for CDK11; heterozygous deletion of chromosome 1p36, which encompasses both CDK11 and CCNL2, sensitizes cancer cells to CDK11 inhibition, establishing CCNL2 as a functional partner required for CDK11 activity in RNA splicing and homologous recombination gene expression.","method":"Integrative functional genomics, genetic and pharmacological CDK11 inhibition, genetically-engineered mouse model, RNA splicing analysis","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — preprint, genomic/genetic inference for CCNL2 role as CDK11 cyclin; direct biochemical reconstitution of CCNL2–CDK11 complex not described in abstract","pmids":[],"is_preprint":true}],"current_model":"CCNL2 (Cyclin L2) acts as an activating cyclin for CDK11, regulating RNA splicing and transcription; its mRNA stability is controlled by YBX1-mediated m5C methylation (with MATR3 as a co-regulator), its transcription is driven by KLF3, and its expression is post-transcriptionally suppressed by miR-214; CCNL2 protein physically associates with lnc-RNU12 in T cells to modulate cell cycle progression, and loss of CCNL2 activity (alone or together with CDK11 deletion) impairs splicing and sensitizes cells to CDK11 inhibition."},"narrative":{"mechanistic_narrative":"CCNL2 (Cyclin L2) is a cell-cycle and RNA-processing regulator that operates as the activating cyclin for the kinase CDK11, where loss of the CCNL2/CDK11 locus on chromosome 1p36 sensitizes cancer cells to CDK11 inhibition and links CCNL2 to RNA splicing and homologous-recombination gene expression. Consistent with a role in cell-cycle control, CCNL2 protein physically associates with the lncRNA lnc-RNU12 in T cells, and depletion of this lncRNA alters CCNL2 levels and causes S-phase arrest [PMID:36165706]. CCNL2 abundance is set by multiple converging regulatory inputs: its mRNA is bound and stabilized by the m5C reader YBX1 in cooperation with MATR3 [PMID:40707993], its transcription is activated by KLF3 [PMID:34937039], and its expression is post-transcriptionally suppressed by miR-214 [PMID:27381447]. Through these inputs CCNL2 promotes cell proliferation and modulates chemoresistance, driving ovarian cancer proliferation and cisplatin resistance [PMID:40707993] and restraining smooth-muscle proliferation when downregulated by miR-214 [PMID:27381447]. Beyond these regulatory and functional associations, direct biochemical reconstitution of the CCNL2 enzymatic role and its structural basis have not been characterized in the available corpus.","teleology":[{"year":2016,"claim":"Established that CCNL2 is a post-transcriptionally controlled regulator whose downregulation drives proliferation, answering whether CCNL2 levels have a defined cellular consequence.","evidence":"Luciferase reporter validation of miR-214 binding plus mimic/inhibitor rescue and proliferation/apoptosis assays in pulmonary artery smooth muscle cells","pmids":["27381447"],"confidence":"Medium","gaps":["Does not identify the molecular effector through which CCNL2 limits proliferation","Restricted to a single cell type under hypoxia"]},{"year":2021,"claim":"Identified KLF3 as a transcriptional activator of CCNL2, addressing how CCNL2 expression is driven at the promoter level.","evidence":"GEO mining, luciferase/binding and rescue experiments along a miR-23a-3p → KLF3 → CCNL2 axis in a spinal cord ischemia/reperfusion model","pmids":["34937039"],"confidence":"Low","gaps":["Mechanistic detail of the KLF3–CCNL2 promoter interaction is limited","Single lab; direct KLF3 occupancy at the CCNL2 promoter not fully resolved"]},{"year":2023,"claim":"Placed CCNL2 in a T-cell cycle-control circuit by showing it is a physical partner of a lncRNA whose loss arrests cells, answering whether CCNL2 protein engages RNA-based regulators.","evidence":"RIP showing lnc-RNU12 interaction with CCNL2 protein plus lncRNA knockdown with S-phase arrest in Jurkat T cells","pmids":["36165706"],"confidence":"Medium","gaps":["Direct functional consequence of the CCNL2–lnc-RNU12 interaction (versus c-JUN co-binding) not separated","No reconstitution of the interaction"]},{"year":2025,"claim":"Defined how CCNL2 mRNA stability is set, showing the m5C reader YBX1 with MATR3 stabilizes the transcript and that CCNL2 drives proliferation and chemoresistance.","evidence":"MeRIP m5C detection, YBX1 reader-residue mutagenesis, YBX1–MATR3 Co-IP and knockdown, with xenograft/PDX and cisplatin sensitivity assays in ovarian cancer","pmids":["40707993"],"confidence":"Medium","gaps":["Single lab; m5C-site mapping on CCNL2 mRNA not detailed","Downstream effectors of CCNL2-driven cisplatin resistance unresolved"]},{"year":2025,"claim":"Assigned CCNL2 a molecular role as the activating cyclin for CDK11, connecting it mechanistically to RNA splicing and a therapeutic vulnerability.","evidence":"Integrative functional genomics, genetic and pharmacological CDK11 inhibition, and a genetically engineered mouse model with RNA splicing analysis (preprint)","pmids":[],"confidence":"Low","gaps":["Preprint; direct biochemical reconstitution of a CCNL2–CDK11 complex not shown","Inference rests on co-deletion of CDK11 and CCNL2 at 1p36 rather than CCNL2-specific perturbation"]},{"year":null,"claim":"The catalytic/structural basis of CCNL2 as a CDK11 cyclin and the direct splicing substrates it controls remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No reconstituted CCNL2–CDK11 kinase complex","No structural model","Direct splicing targets dependent on CCNL2 not enumerated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[2]}],"localization":[],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[4]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[2]}],"complexes":[],"partners":["CDK11","YBX1","MATR3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96S94","full_name":"Cyclin-L2","aliases":["Paneth cell-enhanced expression protein"],"length_aa":520,"mass_kda":58.1,"function":"Regulatory component of the cyclin-L-CDK11 complex that regulates transcription and pre-mRNA splicing (PubMed:14684736, PubMed:18216018, PubMed:36104565, PubMed:38059508). May induce cell death, possibly by acting on the transcription and RNA processing of apoptosis-related factors (PubMed:14684736)","subcellular_location":"Nucleus speckle; Nucleus, nucleoplasm","url":"https://www.uniprot.org/uniprotkb/Q96S94/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CCNL2","classification":"Not Classified","n_dependent_lines":74,"n_total_lines":1208,"dependency_fraction":0.061258278145695365},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CSNK2B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CCNL2","total_profiled":1310},"omim":[{"mim_id":"613482","title":"CYCLIN L2; CCNL2","url":"https://www.omim.org/entry/613482"},{"mim_id":"613384","title":"CYCLIN L1; CCNL1","url":"https://www.omim.org/entry/613384"},{"mim_id":"176873","title":"CYCLIN-DEPENDENT KINASE 11B; CDK11B","url":"https://www.omim.org/entry/176873"},{"mim_id":"116951","title":"CYCLIN-DEPENDENT KINASE 11A; CDK11A","url":"https://www.omim.org/entry/116951"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Vesicles","reliability":"Additional"},{"location":"Basal body","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CCNL2"},"hgnc":{"alias_symbol":["ania-6b","PCEE","SB138","HLA-ISO","CCNS"],"prev_symbol":["CCNM"]},"alphafold":{"accession":"Q96S94","domains":[{"cath_id":"1.10.472.10","chopping":"58-188","consensus_level":"high","plddt":94.6602,"start":58,"end":188},{"cath_id":"1.10.472.10","chopping":"197-286","consensus_level":"high","plddt":95.7603,"start":197,"end":286}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96S94","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96S94-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96S94-F1-predicted_aligned_error_v6.png","plddt_mean":69.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CCNL2","jax_strain_url":"https://www.jax.org/strain/search?query=CCNL2"},"sequence":{"accession":"Q96S94","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96S94.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96S94/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96S94"}},"corpus_meta":[{"pmid":"27381447","id":"PMC_27381447","title":"Upregulation of MicroRNA-214 Contributes to the Development of Vascular Remodeling in Hypoxia-induced Pulmonary Hypertension Via Targeting CCNL2.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27381447","citation_count":30,"is_preprint":false},{"pmid":"16571622","id":"PMC_16571622","title":"CCNs, fibulin-1C and S100A4 expression in leiomyoma and myometrium: inverse association with TGF-beta and regulation by TGF-beta in leiomyoma and myometrial smooth muscle cells.","date":"2006","source":"Molecular human reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/16571622","citation_count":28,"is_preprint":false},{"pmid":"37202628","id":"PMC_37202628","title":"Significance of CCNs in liver regeneration.","date":"2023","source":"Journal of cell communication and signaling","url":"https://pubmed.ncbi.nlm.nih.gov/37202628","citation_count":15,"is_preprint":false},{"pmid":"35674933","id":"PMC_35674933","title":"The role of CCNs in controlling cellular communication in the tumor microenvironment.","date":"2022","source":"Journal of cell communication and signaling","url":"https://pubmed.ncbi.nlm.nih.gov/35674933","citation_count":11,"is_preprint":false},{"pmid":"34937039","id":"PMC_34937039","title":"Exosome miR-23a-3p from Osteoblast Alleviates Spinal Cord Ischemia/Reperfusion Injury by Down-Regulating KLF3-Activated CCNL2 Transcription.","date":"2021","source":"Developmental neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/34937039","citation_count":8,"is_preprint":false},{"pmid":"36165706","id":"PMC_36165706","title":"A novel long non-coding RNA, lnc-RNU12, influences the T-cell cycle via c-JUN and CCNL2 in rheumatoid arthritis.","date":"2023","source":"Rheumatology (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/36165706","citation_count":7,"is_preprint":false},{"pmid":"39800017","id":"PMC_39800017","title":"5-Methylcytosine-modified circRNA-CCNL2 regulates vascular remdeling in hypoxic pulmonary hypertension through binding to FXR2.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/39800017","citation_count":7,"is_preprint":false},{"pmid":"40707993","id":"PMC_40707993","title":"5-methylcytosine regulated CCNL2 promotes tumorigenesis and cisplatin resistance of ovarian cancer with therapeutic implications.","date":"2025","source":"Journal of ovarian research","url":"https://pubmed.ncbi.nlm.nih.gov/40707993","citation_count":4,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.03.668359","title":"On-target toxicity limits the efficacy of CDK11 inhibition against cancers with 1p36 deletions","date":"2025-08-03","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.03.668359","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7213,"output_tokens":1542,"usd":0.022385,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8240,"output_tokens":2184,"usd":0.0479,"stage2_stop_reason":"end_turn"},"total_usd":0.070285,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"CCNL2 is a direct target of miR-214 in pulmonary artery smooth muscle cells (PASMCs); miR-214 binds to CCNL2 mRNA and suppresses its expression, promoting PASMC proliferation by suppressing apoptosis. Hypoxia increases miR-214 and decreases CCNL2, while miR-214 inhibitors reverse this, upregulating CCNL2 and attenuating proliferation.\",\n      \"method\": \"Luciferase reporter assay (target validation), RT-PCR, western blot, miR-214 mimic/inhibitor transfection, cell proliferation and apoptosis assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase assay plus functional rescue in a single lab with two orthogonal methods (reporter + cellular phenotype)\",\n      \"pmids\": [\"27381447\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"KLF3 transcriptionally activates CCNL2 expression; miR-23a-3p (carried in osteoblast exosomes) targets KLF3, thereby suppressing KLF3-driven CCNL2 transcription and alleviating spinal cord ischemia/reperfusion injury. Rescue experiments confirmed the miR-23a-3p → KLF3 → CCNL2 regulatory axis.\",\n      \"method\": \"Co-culture experiments, GEO database mining, exosome treatment of SCIRI cells, luciferase/binding assays, rescue/overexpression experiments, RT-PCR and western blot\",\n      \"journal\": \"Developmental neuroscience\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, functional rescue experiments described but mechanistic detail on KLF3–CCNL2 transcriptional interaction is limited in the abstract\",\n      \"pmids\": [\"34937039\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"lnc-RNU12 physically interacts with cyclin L2 (CCNL2) protein (and c-JUN) in Jurkat T cells, as verified by RNA-binding protein immunoprecipitation (RIP). Knockdown of lnc-RNU12 alters CCNL2 mRNA and protein expression and causes cell cycle S-phase arrest, placing CCNL2 downstream of lnc-RNU12 in T-cell cycle regulation.\",\n      \"method\": \"RNA-binding protein immunoprecipitation (RIP) assay, lncRNA knockdown in Jurkat T cells, cell cycle analysis, RT-PCR, western blot\",\n      \"journal\": \"Rheumatology (Oxford, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP assay plus functional knockdown with defined cell-cycle phenotype, single lab, two orthogonal methods\",\n      \"pmids\": [\"36165706\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"YBX1 directly binds CCNL2 mRNA and stabilizes it via 5-methylcytosine (m5C) modification; mutation of the m5C-reader residue in YBX1 reduces CCNL2 expression. MATR3 interacts with YBX1 and cooperatively regulates CCNL2 levels; MATR3 knockdown reverses YBX1-induced CCNL2 upregulation. CCNL2 promotes ovarian cancer cell proliferation and cisplatin resistance.\",\n      \"method\": \"MeRIP assay (m5C detection), YBX1 mutagenesis, Co-IP (YBX1–MATR3 interaction), siRNA knockdown, xenograft and PDX models, in vitro proliferation and cisplatin sensitivity assays\",\n      \"journal\": \"Journal of ovarian research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MeRIP assay, mutagenesis, and Co-IP in a single lab with multiple orthogonal methods\",\n      \"pmids\": [\"40707993\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CCNL2 is an activating cyclin for CDK11; heterozygous deletion of chromosome 1p36, which encompasses both CDK11 and CCNL2, sensitizes cancer cells to CDK11 inhibition, establishing CCNL2 as a functional partner required for CDK11 activity in RNA splicing and homologous recombination gene expression.\",\n      \"method\": \"Integrative functional genomics, genetic and pharmacological CDK11 inhibition, genetically-engineered mouse model, RNA splicing analysis\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — preprint, genomic/genetic inference for CCNL2 role as CDK11 cyclin; direct biochemical reconstitution of CCNL2–CDK11 complex not described in abstract\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"CCNL2 (Cyclin L2) acts as an activating cyclin for CDK11, regulating RNA splicing and transcription; its mRNA stability is controlled by YBX1-mediated m5C methylation (with MATR3 as a co-regulator), its transcription is driven by KLF3, and its expression is post-transcriptionally suppressed by miR-214; CCNL2 protein physically associates with lnc-RNU12 in T cells to modulate cell cycle progression, and loss of CCNL2 activity (alone or together with CDK11 deletion) impairs splicing and sensitizes cells to CDK11 inhibition.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CCNL2 (Cyclin L2) is a cell-cycle and RNA-processing regulator that operates as the activating cyclin for the kinase CDK11, where loss of the CCNL2/CDK11 locus on chromosome 1p36 sensitizes cancer cells to CDK11 inhibition and links CCNL2 to RNA splicing and homologous-recombination gene expression [#4]. Consistent with a role in cell-cycle control, CCNL2 protein physically associates with the lncRNA lnc-RNU12 in T cells, and depletion of this lncRNA alters CCNL2 levels and causes S-phase arrest [#2]. CCNL2 abundance is set by multiple converging regulatory inputs: its mRNA is bound and stabilized by the m5C reader YBX1 in cooperation with MATR3 [#3], its transcription is activated by KLF3 [#1], and its expression is post-transcriptionally suppressed by miR-214 [#0]. Through these inputs CCNL2 promotes cell proliferation and modulates chemoresistance, driving ovarian cancer proliferation and cisplatin resistance [#3] and restraining smooth-muscle proliferation when downregulated by miR-214 [#0]. Beyond these regulatory and functional associations, direct biochemical reconstitution of the CCNL2 enzymatic role and its structural basis have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Established that CCNL2 is a post-transcriptionally controlled regulator whose downregulation drives proliferation, answering whether CCNL2 levels have a defined cellular consequence.\",\n      \"evidence\": \"Luciferase reporter validation of miR-214 binding plus mimic/inhibitor rescue and proliferation/apoptosis assays in pulmonary artery smooth muscle cells\",\n      \"pmids\": [\"27381447\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not identify the molecular effector through which CCNL2 limits proliferation\", \"Restricted to a single cell type under hypoxia\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified KLF3 as a transcriptional activator of CCNL2, addressing how CCNL2 expression is driven at the promoter level.\",\n      \"evidence\": \"GEO mining, luciferase/binding and rescue experiments along a miR-23a-3p \\u2192 KLF3 \\u2192 CCNL2 axis in a spinal cord ischemia/reperfusion model\",\n      \"pmids\": [\"34937039\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Mechanistic detail of the KLF3\\u2013CCNL2 promoter interaction is limited\", \"Single lab; direct KLF3 occupancy at the CCNL2 promoter not fully resolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Placed CCNL2 in a T-cell cycle-control circuit by showing it is a physical partner of a lncRNA whose loss arrests cells, answering whether CCNL2 protein engages RNA-based regulators.\",\n      \"evidence\": \"RIP showing lnc-RNU12 interaction with CCNL2 protein plus lncRNA knockdown with S-phase arrest in Jurkat T cells\",\n      \"pmids\": [\"36165706\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct functional consequence of the CCNL2\\u2013lnc-RNU12 interaction (versus c-JUN co-binding) not separated\", \"No reconstitution of the interaction\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined how CCNL2 mRNA stability is set, showing the m5C reader YBX1 with MATR3 stabilizes the transcript and that CCNL2 drives proliferation and chemoresistance.\",\n      \"evidence\": \"MeRIP m5C detection, YBX1 reader-residue mutagenesis, YBX1\\u2013MATR3 Co-IP and knockdown, with xenograft/PDX and cisplatin sensitivity assays in ovarian cancer\",\n      \"pmids\": [\"40707993\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab; m5C-site mapping on CCNL2 mRNA not detailed\", \"Downstream effectors of CCNL2-driven cisplatin resistance unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Assigned CCNL2 a molecular role as the activating cyclin for CDK11, connecting it mechanistically to RNA splicing and a therapeutic vulnerability.\",\n      \"evidence\": \"Integrative functional genomics, genetic and pharmacological CDK11 inhibition, and a genetically engineered mouse model with RNA splicing analysis (preprint)\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Preprint; direct biochemical reconstitution of a CCNL2\\u2013CDK11 complex not shown\", \"Inference rests on co-deletion of CDK11 and CCNL2 at 1p36 rather than CCNL2-specific perturbation\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The catalytic/structural basis of CCNL2 as a CDK11 cyclin and the direct splicing substrates it controls remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No reconstituted CCNL2\\u2013CDK11 kinase complex\", \"No structural model\", \"Direct splicing targets dependent on CCNL2 not enumerated\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CDK11\", \"YBX1\", \"MATR3\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}