{"doi":"10.1101/2021.06.04.446938","title":"Prenatal cadmium exposure alters proliferation in mouse CD4 <sup>+</sup> T cells via LncRNA Snhg7","abstract":"ABSTRACT Objective Prenatal cadmium (Cd) exposure leads to immunotoxic phenotypes in the offspring affecting coding and non-coding genes. Recent studies have shown that long non-coding RNAs (lncRNAs) are integral to T cell regulation. Here, we investigated the role of long non-coding RNA small nucleolar RNA hostgene 7 (lncSnhg7) in T cell proliferation. Methods RNA sequencing was used to analyze the expression of lncRNAs in splenic CD4 + T cells with and without CD3/CD28 stimulation. Next, T cells isolated from offspring exposed to control or Cd water throughout mating and gestation were analyzed with and without stimulation with anti-CD3/CD28 beads. Quantitative qPCR and western blotting were used to detect RNA and protein levels of specific genes. Overexpression of a miR-34a mimic was achieved using nucleofection. Apoptosis was measured using flow cytometry and luminescence assays. Flow cytometry was also used to measure T cell proliferation in culture. Results We identified 23 lncRNAs that were differentially expressed in stimulated versus unstimulated T cells, including lncSnhg7. LncSnhg7 and a downstream protein, GALNT7, are upregulated in T cells from offspring exposed to Cd during gestation. Overexpression of miR-34a, a regulator of lncSnhg7 and GALNT7, suppresses GALNT7 protein levels in primary T cells, but not in a mouse T lymphocyte cell line. The T cells isolated from Cd-exposed offspring exhibit increased proliferation after activation in vitro , but Treg suppression and CD4 + T cell apoptosis are not affected by prenatal Cd exposure. Conclusion Prenatal Cd exposure alters the expression of lncRNAs during T cell activation. The induction of lncSnhg7 is enhanced in splenic T cells from Cd offspring resulting in the upregulation of GALNT7 protein and increased proliferation following activation. miR-34a overexpression decreased GALNT7 expression suggesting that the lncSnhg7/miR-34a/GALNT7 is an important pathway in primary CD4 + T cells. These data highlight the need to understand the consequences of environmental exposures on lncRNA functions in non-cancerous cells as well as the effects in utero .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":224873,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9629,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":399397,"name":"Melinda E. Varney","orcid":"0000-0001-9616-4808","position":1,"is_corresponding":false},{"id":827112,"name":"Sebastian A. Dziadowicz","orcid":"0000-0001-6277-9310","position":2,"is_corresponding":false},{"id":789969,"name":"Casey Hall","orcid":"0000-0002-4294-6131","position":3,"is_corresponding":false},{"id":740876,"name":"Kathryn E. Blethen","orcid":"0000-0003-4602-9514","position":4,"is_corresponding":false},{"id":331852,"name":"Gangqing Hu","orcid":"0000-0001-5453-6888","position":5,"is_corresponding":false},{"id":425761,"name":"John B. Barnett","orcid":"0000-0001-6547-2381","position":6,"is_corresponding":false},{"id":827113,"name":"Ivan Martinez","orcid":"0000-0002-2187-5119","position":7,"is_corresponding":false},{"id":789968,"name":"Jamie L. McCall","orcid":"0000-0001-5914-6336","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T23:54:22.889584Z","pmid":null,"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":[]}