{"doi":"10.7554/elife.102681","title":"The long noncoding RNA lnc-FANCI-2 intrinsically restricts RAS signaling in human papillomavirus type 16-infected cervical cancer cells","abstract":"Increased expression of lnc-FANCI-2, a newly discovered long noncoding RNA, is associated with cervical lesion progression from cervical intraepithelial neoplasia stage 1 (CIN1, low grade), CIN2–3 (high grade), to cervical cancer. Viral oncoprotein E7 of high-risk human papillomaviruses (HR-HPVs) and host transcription factor YY1 are two major factors promoting lnc-FANCI-2 expression. Using CRISPR-Cas9 technology, we knocked out the expression of lnc-FANCI-2 in the HPV16-positive cervical cancer cell line, CaSki cells. The selected knockout (KO) single-cell clones displayed altered cell morphology and proliferation with changes of cellular soluble receptors, but normal HPV16 E6 and E7 expression. Relative to the parental cells, lnc-FANCI-2 KO cells exhibited significantly increased RAS signaling and epithelial-mesenchymal transition, but decreased response to IFN signaling, along with increased p-Akt and p-Erk1/2 (two RAS signaling effectors), IGFBP3, MCAM, VIM, and CCND2 (cyclin D2) and decreased expression of RAC3. lnc-FANCI-2 in CaSki interacts with cellular proteins H13, HNRH1, K1H1, MAP4K4, and RNPS1. MAP4K4 knockdown led to enhance the expression of p-Erk1/2 and p-Akt. High lnc-FANCI-2 and low MCAM levels in cervical cancer tissues were found to be associated with patients’ survival. A key function of lnc-FANCI-2 intrinsically regulates RAS signaling to impact cervical lesion progression and cervical cancer prognosis.","journal":"eLife","year":2024,"id":489327,"datarank":0.1719769055377281,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.007185062237511627,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.007185062237511627,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE190904"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":562955,"name":"Lulu Yu","orcid":"0000-0003-0309-9520","position":1,"is_corresponding":false},{"id":328278,"name":"Vladimır Majerčiak","orcid":"0000-0003-2907-4583","position":2,"is_corresponding":false},{"id":500995,"name":"Thomas J. Meyer","orcid":"0000-0002-7185-5597","position":3,"is_corresponding":false},{"id":233729,"name":"Ming Yi","orcid":"0000-0001-9098-1364","position":4,"is_corresponding":false},{"id":477626,"name":"Peter F. Johnson","orcid":"0000-0002-4145-4725","position":5,"is_corresponding":false},{"id":562958,"name":"Maggie Cam","orcid":"0000-0001-8190-9766","position":6,"is_corresponding":false},{"id":218030,"name":"Douglas R. Lowy","orcid":"0000-0003-0635-219X","position":7,"is_corresponding":false},{"id":219079,"name":"Zhi-Ming Zheng","orcid":"0000-0001-5547-7912","position":8,"is_corresponding":false},{"id":562957,"name":"Haibin Liu","orcid":"0000-0003-3601-6066","position":0,"is_corresponding":true}],"reference_count":112,"raw_metadata":null,"created_at":"2026-07-19T02:08:23.929823Z","pmid":"40878909","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}