A short peptide encoded by long non‐coding <scp>RNA</scp> small nucleolar <scp>RNA</scp> host gene 6 promotes cell migration and epithelial–mesenchymal transition by activating transforming growth factor‐beta/<scp>SMAD</scp> signaling pathway in human endometrial cells

Zhou, Qian; Du, Xin; Zhou, Limin; Yao, Dongmei; Dong, Yi; Jin, Jing

doi:10.1111/jog.15476

Cited by 7 publications

(2 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further studies are warranted to determine whether the observed function of SNHG6 was caused by the lncRNA itself, or by its contained snoRNA. Additionally, there is recent evidence that SNHG6 encodes for a small peptide that may be functional [ 79 ].…”

Section: Discussionmentioning

confidence: 99%

Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia

Hazan,

Amador,

Ali-Nasser

et al. 2024

J Biomed Sci

View full text Add to dashboard Cite

Background Long non-coding RNAs (lncRNAs) are pivotal players in cellular processes, and their unique cell-type specific expression patterns render them attractive biomarkers and therapeutic targets. Yet, the functional roles of most lncRNAs remain enigmatic. To address the need to identify new druggable lncRNAs, we developed a comprehensive approach integrating transcription factor binding data with other genetic features to generate a machine learning model, which we have called INFLAMeR (Identifying Novel Functional LncRNAs with Advanced Machine Learning Resources). Methods INFLAMeR was trained on high-throughput CRISPR interference (CRISPRi) screens across seven cell lines, and the algorithm was based on 71 genetic features. To validate the predictions, we selected candidate lncRNAs in the human K562 leukemia cell line and determined the impact of their knockdown (KD) on cell proliferation and chemotherapeutic drug response. We further performed transcriptomic analysis for candidate genes. Based on these findings, we assessed the lncRNA small nucleolar RNA host gene 6 (SNHG6) for its role in myeloid differentiation. Finally, we established a mouse K562 leukemia xenograft model to determine whether SNHG6 KD attenuates tumor growth in vivo. Results The INFLAMeR model successfully reconstituted CRISPRi screening data and predicted functional lncRNAs that were previously overlooked. Intensive cell-based and transcriptomic validation of nearly fifty genes in K562 revealed cell type-specific functionality for 85% of the predicted lncRNAs. In this respect, our cell-based and transcriptomic analyses predicted a role for SNHG6 in hematopoiesis and leukemia. Consistent with its predicted role in hematopoietic differentiation, SNHG6 transcription is regulated by hematopoiesis-associated transcription factors. SNHG6 KD reduced the proliferation of leukemia cells and sensitized them to differentiation. Treatment of K562 leukemic cells with hemin and PMA, respectively, demonstrated that SNHG6 inhibits red blood cell differentiation but strongly promotes megakaryocyte differentiation. Using a xenograft mouse model, we demonstrate that SNHG6 KD attenuated tumor growth in vivo. Conclusions Our approach not only improved the identification and characterization of functional lncRNAs through genomic approaches in a cell type-specific manner, but also identified new lncRNAs with roles in hematopoiesis and leukemia. Such approaches can be readily applied to identify novel targets for precision medicine.

show abstract

Section: Discussionmentioning

confidence: 99%

Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia

Hazan,

Amador,

Ali-Nasser

et al. 2024

J Biomed Sci

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia

Hazan,

Amador,

Lahav

et al. 2023

Preprint

View full text Add to dashboard Cite

BackgroundLong non-coding RNAs (lncRNAs) are pivotal players in cellular processes, and their unique cell-type specific expression patterns make them attractive biomarkers and therapeutic targets. Yet, the functional roles of most lncRNAs remain enigmatic. To address the need to identify new druggable lncRNAs, we developed a comprehensive approach integrating transcription factor binding data with other genetic features to generate a machine learning model, which we have called INFLAMeR (Identifying Novel Functional LncRNAs with Advanced Machine Learning Resources).MethodsINFLAMeR was trained on high-throughput CRISPR interference (CRISPRi) screens across seven cell lines, and the algorithm was based on 71 genetic features. To validate the predictions, we selected candidate lncRNAs in the K562 leukemia cell line and determined the effect of their knockdown on cell proliferation and chemotherapy drug resistance. We further performed transcriptomic analysis for candidate genes. Based on these findings, we assessed the lncRNA Small Nucleolar RNA Host Gene 6 (SNHG6) for its role in myeloid differentiation by incubation with Phorbol 12-myristate 13-acetate (PMA) to induce megakaryocyte differentiation, or with hemin to induce erythrocyte differentiation.ResultsThe INFLAMeR model successfully reconstituted CRISPRi screening data and predicted functional lncRNAs that were previously overlooked. Intensive cell-based and transcriptomic validation of nearly fifty genes in K562 revealed cell type-specific functionality for 85% of the predicted lncRNAs. Our cell-based and transcriptomic analyses predicted a role for SNHG6 in hematopoiesis and leukemia. Consistent with its predicted role in hematopoietic differentiation,SNHG6transcription is regulated by hematopoiesis-associated transcription factors. Knockdown of SNHG6 reduced the proliferation of leukemia cells and sensitized them to differentiation. Treatment of K562 leukemic cells with hemin and PMA, respectively, demonstrated that SNHG6 inhibits red blood cell differentiation but strongly promotes megakaryocyte differentiation. DespiteSNHG6transcripts showing strong cytoplasmic enrichment,SNHG6regulates the expression of hematopoietic genes such asPPBP(Pro-Platelet Basic Protein) andPF4(Platelet Factor 4).ConclusionsOur approach not only improved the identification and characterization of functional lncRNAs through genomic approaches in a cell type-specific manner, but also identified new lncRNAs with a role in hematopoiesis and leukemia. Such approaches cab be used to identify new targets for precision therapy.

show abstract

The lncRNA LINC00339-encoded peptide promotes trophoblast adhesion to endometrial cells via MAPK and PI3K-Akt signaling pathways

Zhou,

Yu,

Zhao

et al. 2023

J Assist Reprod Genet

View full text Add to dashboard Cite

A short peptide encoded by long non‐coding RNA small nucleolar RNA host gene 6 promotes cell migration and epithelial–mesenchymal transition by activating transforming growth factor‐beta/SMAD signaling pathway in human endometrial cells

Cited by 7 publications

References 51 publications

Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia

Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia

Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia

The lncRNA LINC00339-encoded peptide promotes trophoblast adhesion to endometrial cells via MAPK and PI3K-Akt signaling pathways

Contact Info

Product

Resources

About