Identification and roles of mir-29b-1-3p and mir29a-3p-regulated and non-regulated lncrnas in endocrine-sensitive and resistant breast cancer cells

Penn Muluhngwi, Carolyn M. Klinge

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17 Scopus citations

Abstract

Despite improvements in the treatment of endocrine-resistant metastatic disease using combination therapies in patients with estrogen receptor α (ERα) primary tumors, the mechanisms underlying endocrine resistance remain to be elucidated. Non-coding RNAs (ncRNAs), including microRNAs (miRNA) and long non-coding RNAs (lncRNA), are targets and regulators of cell signaling pathways and their exosomal transport may contribute to metastasis. Previous studies have shown that a low expression of miR-29a-3p and miR-29b-3p is associated with lower overall breast cancer survival before 150 mos. Transient, modest overexpression of miR-29b1-3p or miR-29a-3p inhibited MCF-7 tamoxifen-sensitive and LCC9 tamoxifen-resistant cell proliferation. Here, we identify miR-29b-1/a-regulated and non-regulated differentially expressed lncRNAs in MCF-7 and LCC9 cells using next-generation RNA seq. More lncRNAs were miR-29b-1/a-regulated in LCC9 cells than in MCF-7 cells, including DANCR, GAS5, DSCAM-AS1, SNHG5, and CRND. We exam-ined the roles of miR-29-regulated and differentially expressed lncRNAs in endocrine-resistant breast cancer, including putative and proven targets and expression patterns in survival analysis using the KM Plotter and TCGA databases. This study provides new insights into lncRNAs in en-docrine-resistant breast cancer.

Original languageEnglish (US)
Article number3530
JournalCancers
Volume13
Issue number14
DOIs
StatePublished - Jul 2 2021
Externally publishedYes

Bibliographical note

Funding Information:
Supplementary Materials: The following are available online: www.mdpi.com/article/10.3390/cancers13143530/s1. Table S1: GO Processes for miR-29b-1-3p/miR-29a-3p-down-regulated lncRNAs in MCF-7 and LCC9 cells from Table 1 were identified by MetaCore. Table S2: Networks and GO Processes identified for miR-29b-1-3p/miR-29a-3p-down-regulated lncRNAs in MCF-7 and LCC9 cells from Table 1 were identified by MetaCore. Table S3: GO Processes for miR-29b-1-3p/miR-29a-3p-down-regulated lncRNAs in MCF-7 and LCC9 cells from Table 1 were identified by MetaCore. Table S4: Networks and GO Processes identified for miR-29b-1-3p/miR-29a-3p-down-regulated lncRNAs in MCF-7 and LCC9 cells from Table 1 were identified by MetaCore. Table S5: lncRNAs differentially expressed in MCF-7 and LCC9 cells that were not regulated by miR-29b-1-3p/miR-29a-3p-with low expression < 1 FPKM. Values are FPKM and are the average of 15 biological replicates +/-Standard deviation. Table S6: GO Processes for lncRNAs differentially expressed in MCF-7 and LCC9 cells from Table 3 were identified by MetaCore. Table S7: Networks and GO Processes identified for miR-29b-1-3p/miR-29a-3p-down-regulated lncRNAs in MCF-7 and LCC9 cells from Table 1 were identified by MetaCore. References [275–286] were cited in Supplementary Materials. Author Contributions: P.M. performed the cell experiments (while a graduate student at the University of Louisville), analyzed data, contributed to writing on lncRNAs in Table 3, and edited the manuscript. C.M.K. analyzed data and wrote the manuscript. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by NIH R01 CA138410. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: GEO accession # GSE81620 Conflicts of Interest: The authors declare no conflict of interest.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Breast cancer
  • Endocrine resistance
  • LncRNA
  • MiR-29
  • Tamoxifen

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