Joint changes in RNA, RNA polymerase II, and promoter activity through the cell cycle identify non-coding RNAs involved in proliferation

Abstract

Proper regulation of the cell cycle is necessary for normal growth and development of all organisms. Conversely, altered cell cycle regulation often underlies proliferative diseases such as cancer. Long non-coding RNAs (lncRNAs) are recognized as important regulators of gene expression and are often found dysregulated in diseases, including cancers. However, identifying lncRNAs with cell cycle functions is challenging due to their often low and cell-type specific expression. We present a highly effective method that analyses changes in promoter activity, transcription, and RNA levels for identifying genes enriched for cell cycle functions. Specifically, by combining RNA sequencing with ChIP sequencing through the cell cycle of synchronized human keratinocytes, we identified 1009 genes with cell cycle-dependent expression and correlated changes in RNA polymerase II occupancy or promoter activity as measured by histone 3 lysine 4 trimethylation (H3K4me3). These genes were highly enriched for genes with known cell cycle functions and included 57 lncRNAs. We selected four of these lncRNAs—SNHG26, EMSLR, ZFAS1, and EPB41L4A-AS1—for further experimental validation and found that knockdown of each of the four lncRNAs affected cell cycle phase distributions and reduced proliferation in multiple cell lines. These results show that many genes with cell cycle functions have concomitant cell-cycle dependent changes in promoter activity, transcription, and RNA levels and support that our multi-omics method is well suited for identifying lncRNAs involved in the cell cycle.

Prognostic implications of necroptosis-related long noncoding RNA signatures in muscle-invasive bladder cancer

“…With reference to EMSLR, it was proved to be essential for tumor-related phenotype. Cell-cycle phase distribution and proliferation reduction can be observed in lung cancer and colon cancer when depleting it (Hegre et al, 2021;Priyanka et al, 2022). Additionally, we estimated the expression of these several prognostic NLRs and found that it was basically consistent with the former bioinformatic analysis.…”

Comprehensive characterization of stemness-related lncRNAs in triple-negative breast cancer identified a novel prognostic signature related to treatment outcomes, immune landscape analysis and therapeutic guidance: a silico analysis with in vivo experiments

“…Liao et al, reported that lncRNA FRGCA was highly expressed in colon adenocarcinoma and correlated with poor prognosis [ 56 ]. Hegre, S et al, reported that an oncogenic role of EMSLR, possibly by interfering with the progression from G1 to the S phase of the cell cycle [ 57 ]. Zhou et al, reported that MIR193BHG was one of the six pyroptosis-related lncRNAs prognostic signature for renal clear cell cancer prognosis prediction [ 58 ].…”

A cuproptosis-related lncRNA signature to predict prognosis and immune microenvironment of colon adenocarcinoma

“…(2) Jiang et al revealed that SNHG26 stimulated PGK1/AKT/mTOR signaling pathway to promote tumor growth, metastasis, and chemotherapy resistance 41 . Hegre et al illuminated that knockdown of SNHG26 could interfere with the phase distributions of the cell cycle and reduce cell proliferation 42 . It is worth noting that a recent study analogously used SNHG26 to establish a prognostic signature of tumor immune infiltration-related lncRNAs in colon cancer, which confirmed the indispensable role of SNHG26 in the prognosis 43 .…”