Approaches to Identify and Characterise the Post-Transcriptional Roles of lncRNAs in Cancer

Carter, Jean-Michel; Ang, Daniel Aron; Sim, Nicholas; Budiman, Andrea; Li, Yinghui

doi:10.3390/ncrna7010019

Cited by 9 publications

(8 citation statements)

References 254 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we identified mRNAs bound to biotin-tagged miRNA mimics within cells using RNA-seq [ 36 ]. This technique is increasingly common, particularly in the context of assessing the lncRNA-miRNA interactions which are likely to be relatively stable and therefore experimentally more amenable [ 45 ], but has not previously been attempted for either miR-195 or miR-26b. To our surprise, through this and the prediction of miRNA binding sites, we identified the same shared target for both our miRNAs, namely semaphorin A6D (SEMA6D).…”

Section: Discussionmentioning

confidence: 99%

MiR-195 and Its Target SEMA6D Regulate Chemoresponse in Breast Cancer

Baxter

Allinson

Amri

et al. 2021

Cancers

View full text Add to dashboard Cite

Background: poor prognosis primary breast cancers are typically treated with cytotoxic chemotherapy. However, recurrences remain relatively common even after this aggressive therapy. Comparison of matched tumours pre- and post-chemotherapy can allow identification of molecular characteristics of therapy resistance and thereby potentially aid discovery of novel predictive markers or targets for chemosensitisation. Through this comparison, we aimed to identify microRNAs associated with chemoresistance, define microRNA target genes, and assess targets as predictors of chemotherapy response. Methods: cancer cells were laser microdissected from matched breast cancer tissues pre- and post-chemotherapy from estrogen receptor positive/HER2 negative breast cancers showing partial responses to epirubicin/cyclophosphamide chemotherapy (n = 5). MicroRNA expression was profiled using qPCR arrays. MicroRNA/mRNA expression was manipulated in estrogen receptor positive/HER2 negative breast cancer cell lines (MCF7 and MDA-MB-175 cells) with mimics, inhibitors or siRNAs, and chemoresponse was assessed using MTT and colony forming survival assays. MicroRNA targets were identified by RNA-sequencing of microRNA mimic pull-downs, and comparison of these with mRNAs containing predicted microRNA binding sites. Survival correlations were tested using the METABRIC expression dataset (n = 1979). Results: miR-195 and miR-26b were consistently up-regulated after therapy, and changes in their expression in cell lines caused significant differences in chemotherapy sensitivity, in accordance with up-regulation driving resistance. SEMA6D was defined and confirmed as a target of the microRNAs. Reduced SEMA6D expression was significantly associated with chemoresistance, in accordance with SEMA6D being a down-stream effector of the microRNAs. Finally, low SEMA6D expression in breast cancers was significantly associated with poor survival after chemotherapy, but not after other therapies. Conclusions: microRNAs and their targets influence chemoresponse, allowing the identification of SEMA6D as a predictive marker for chemotherapy response that could be used to direct therapy or as a target in chemosensitisation strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

MiR-195 and Its Target SEMA6D Regulate Chemoresponse in Breast Cancer

Baxter

Allinson

Amri

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…More than 28,000 lncRNAs have been discovered, and there are still many lncRNAs to be discovered and annotated. lncRNAs are involved in the malignant biological behavior of tumors and the regulation of chemoresistance [30]. SNHG16 has been upregulated and downregulated in multiple cancers and participates in cell proliferation, migration, invasion and EMT [31].…”

Section: Discussionmentioning

confidence: 99%

PRPF6 promotes metastasis and paclitaxel resistance of ovarian cancer via SNHG16/CEBPB/GATA3 axis

Wang

Zhou

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Metastasis and paclitaxel (PTX) resistance are the main reason for the poor prognosis of ovarian cancer (OC). Evidence has shown that RNA-binding proteins (RBPs) and long noncoding RNAs (lncRNAs) can modulate post-transcriptional regulation. The aim of this study was to determine the relationship among RBP, lncRNA and OC and to further guide clinical therapy. Methods: The expression of pre‐mRNA processing factor 6 (PRPF6) in OC tissues form 68 patients were detected by Immunohistochemistry. The expression of small nucleolar RNA host gene 16(SNHG16) transcripts-SNHG16-L/S in OC cell lines were analyzed by real-time PCR (RT-PCR). Transwell, CCK8 assays and flow cytometry analyses were used to detected effects of PRPF6 and SNHG16 on tumorigenesis and PTX-resistance. Molecular interactions were examined by dual‐luciferase reporter gene assay, RNA immunoprecipitation and chromatin immunoprecipitation. OC cells that knockdown PRPF6 were injected subcutaneously in nude mice.Results: The results showed that PRPF6 was upregulated in OC chemoresistant tissues and was closely related to advanced FIGO stages. PRPF6 promoted progression, and PTX resistance in vitro and in vivo. SNHG16-L/S were differentially expressed in OC cells and tissues as detected through real-time PCR (RT-PCR). SNHG16-L/S had opposite effects on progression and PTX resistance in OC. Mechanistically, SNHG16-L inhibited GATA-binding protein 3 (GATA3) transcription by binding to CCAAT/enhancer-binding protein B (CEBPB). Moreover, PRPF6 induced the alternative splicing of SNHG16, causing downregulation of SNHG16-L and, leading to the upregulation of GATA3 expression to further promote metastasis and PTX-resistance in OC.Conclusions: Totally, these data unveiled that PRPF6 promotes metastasis and PTX resistance of OC through SNHG16-L/CEBPB/GATA3 axis, which provides a new direction for OC treatment.

show abstract

“…When quantifying HSAT1 transcripts, we analyzed cancer cell lines from similar origins with astounding different profiles. In cancer, ncRNAs and tumor suppressor genes/oncogenes share the trait of highly variable transcription, which can indicate the presence of post-transcriptional complexed-regulated pathways (Carter et al 2021). Furthermore, the tendency for mutation of genomic regulators in diseases such as cancer could have a determining role in ncRNA transcription deregulation (Zhou et al 2016; Pratt and Weng 2018; Carter et al 2021).…”

Section: Discussionmentioning

confidence: 99%

Human Satellite 1 (HSAT1) analysis provides novel evidence of pericentromeric transcription

Lopes¹,

Louzada²,

Ferreira³

et al. 2022

Preprint

View full text Add to dashboard Cite

Pericentromeric regions of human chromosomes are composed of tandem-repeated and highly organized sequences named satellite DNAs. Although being known for a long time as the most AT-rich fraction of the human genome, classical satellite HSAT1 has been disregarded in genomic and transcriptional studies, falling behind other human satellites in terms of knowledge. The path followed herein trails with HSAT1 isolation and cloning, followed by in silico analysis. Monomer copy number and expression data was obtained in a wide variety of human cell lines, with greatly varying profiles in tumoral/non-tumoral samples. HSAT1 was mapped in human chromosomes and applied in in situ transcriptional assays. Additionally, it was possible to observe the nuclear organization of HSAT1 transcripts and further characterize them by 3′ RACE-Seq. Size-varying polyadenylated HSAT1 transcripts were detected, which possibly accounts for the intricate regulation of alternative polyadenylation. As far as we know, this work pioneers HSAT1 transcription studies. With the emergence of new human genome assemblies, acrocentric pericentromeres are becoming relevant characters in disease and other biological contexts. HSAT1 sequences and associated noncoding RNAs will most certainly prove significant in the future of HSAT research.

show abstract

Approaches to Identify and Characterise the Post-Transcriptional Roles of lncRNAs in Cancer

Cited by 9 publications

References 254 publications

MiR-195 and Its Target SEMA6D Regulate Chemoresponse in Breast Cancer

MiR-195 and Its Target SEMA6D Regulate Chemoresponse in Breast Cancer

PRPF6 promotes metastasis and paclitaxel resistance of ovarian cancer via SNHG16/CEBPB/GATA3 axis

Human Satellite 1 (HSAT1) analysis provides novel evidence of pericentromeric transcription

Contact Info

Product

Resources

About