lncRNA HAND2‐AS1 overexpression inhibits cancer cell proliferation in hepatocellular carcinoma by downregulating RUNX2 expression

Jing, Guiying; Zheng, Xuan-Zhen; Ji, Xiao-Xia

doi:10.1002/jcla.23717

Cited by 17 publications

(12 citation statements)

References 16 publications

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“…HAND2-AS1 has been reported to be required for the self-renewal maintenance of liver cancer stem cells to initiate liver cancer development ( 40 ). Furthermore, HAND2-AS1 overexpression has been shown to inhibit cancer cell proliferation in liver cancer via the downregulation of runt-related transcription factor 2 expression ( 41 ). ST8SIA6-AS1 has been reported to be a cancer-associated lncRNA that facilitates cell proliferation and resistance to apoptosis in liver cancer cells ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of multiple transcriptomic data identifies ST8SIA6‑AS1 and LINC01093 as potential biomarkers in HBV‑associated liver cancer

Xue¹,

Zhao²,

Fu³

et al. 2023

Oncol Lett

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The mechanisms of long-non-coding RNAs (lncRNAs) in hepatitis B virus (HBV) infection-associated liver cancer remain largely unclear. Therefore, the aim of the present study was to investigate the regulatory mechanisms of lncRNAs in this disease. HBV-liver cancer related transcriptome expression profile data (GSE121248 and GSE55092) from the Gene Expression Omnibus database and survival prognosis information from The Cancer Genome Atlas (TCGA) database were obtained for analysis. The limma package was used to identify the overlapped differentially expressed RNAs (DERs), including DElncRNAs and DEmRNAs, in the GSE121248 and GSE55092 datasets. The screened optimized lncRNA signatures were used to develop a nomogram model based on the GSE121248 dataset, which was validated using the GSE55092 and TCGA datasets. A competitive endogenous RNA (ceRNA) network was constructed based on the screened prognosis-associated lncRNA signatures from TCGA dataset. In addition, the levels of specific lncRNAs were evaluated in HBV-infected human liver cancer tissues and cells, and Cell Counting Kit-8, ELISA and Transwell assays were performed to evaluate the effects of the lncRNAs in HBV-expressing liver cancer cells. A total of 535 overlapped DERs, including 30 DElncRNAs and 505 DEmRNAs, were identified in the GSE121248 and GSE55092 datasets. An optimized DElncRNA signature comprising 10 lncRNAs was used to establish a nomogram. ST8SIA6-AS1 and LINC01093 were identified as lncRNAs associated with HBV-liver cancer prognosis in TCGA dataset, and were applied to construct a ceRNA network. Reverse transcription-quantitative PCR analysis showed that ST8SIA6-AS1 was upregulated and LINC01093 was downregulated in HBV-infected human liver cancer tissues and HBV-expressing liver cancer cells compared with non-HBV-infected controls. ST8SIA6-AS1 knockdown and LINC01093 overexpression independently reduced the number of copies of HBV DNA, the levels of hepatitis B surface antigen and hepatitis B e antigen, as well as cell proliferation, migration and invasion. In summary, the present study identified ST8SIA6-AS1 and LINC01093 as two potential biomarkers that may be effective therapeutic targets for HBV-associated liver cancer.

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Section: Discussionmentioning

confidence: 99%

Integrated analysis of multiple transcriptomic data identifies ST8SIA6‑AS1 and LINC01093 as potential biomarkers in HBV‑associated liver cancer

Xue¹,

Zhao²,

Fu³

et al. 2023

Oncol Lett

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“…Interestingly, HAND2 and its associated lncRNA, HAND2-AS1, were implicated in alleviating numerous human pathologies reviewed in 53,54 . It is reasonable that HAND-AS1-induced MET can be a shared underlying mechanism initiating atherosclerosis prevention 66,67 , impairment of fibroblast activation in rheumatoid arthritis 68 , and inhibition of glioma 69 , prostate 70 , ovarian 71,72 , gastric 73 , bladder 74 , cervical 75,76 , breast 77 , and pancreatic 78 cancer progression with mixed reports in liver cancer [79][80][81] .…”

Section: Discussionmentioning

confidence: 99%

Distinct HAND2/HAND2-AS1 Expression Levels Finetune Mesenchymal and Epithelial Cell Plasticity in Human Mesenchymal Stem Cells

Vazana-Netzarim,

Elmalem,

Sofer

et al. 2023

Preprint

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We have previously developed several successful decellularization strategies yielding porcine cardiac extracellular matrices (pcECMs), which exhibit tissue-specific bioactivity and bioinductive capacity when cultured with various pluri- and multipotent stem cells. Here, we studied the tissue-specific effects of the pcECM on seeded human mesenchymal stem cells (hMSCs) phenotype using reverse transcribed quantitative polymerase chain reaction (RT-qPCR) arrays for cardio-vascular related genes. We further corroborated interesting findings at the protein level (flow cytometry and immunological stains) as well as bioinformatically using several mRNA sequencing and protein databases of normal and pathologic adult tissue expression, as well as during human embryonic organogenesis. We discovered that upon seeding of human mesenchymal stem cells (hMSCs) on the pcECM they displayed partial MET toward endothelial phenotypes (CD31+) and morphologies, which were preceded by an early spike (~day 3 onward after seeding) in HAND2 expression at both the mRNA and protein levels compared to plate controls. CRISPR-Cas9 knockout (KO) of HAND2 and its associated antisense long non-coding RNA (HAND2-AS1) regulatory region resulted in proliferation arrest, hypertrophy, and senescent-like morphology. Bioinformatic analyses revealed that HAND2 and HAND2-AS1 are highly correlated in expression, are expressed in many different tissue types albeit at distinct yet tightly regulated expression levels. Deviation (down or up regulation) from these basal tissue expression levels are associated with a long list of pathologies. We thus suggest that HAND2 expression levels may finetune cell plasticity possibly affecting senescence and mesenchymal-to-epithelial transition states, through yet unknown mechanisms. Targeting this pathway may represent a promising new therapeutic approach for a wide range of diseases, including cancer, degenerative disorders, and aging. Nevertheless, further investigations are required to better understand the molecular players involved, potential inducers and inhibitors of this pathway, and eventually potential therapeutic applications.

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“…Due to this review being focused on TICs, more details about TICs and non-coding RNAs are described (such as ( Huang et al, 2018 ; Machida, 2020 ; Rojas et al, 2022 ): More details about TICs and non-coding RNAs are included such as: ( Huang et al, 2018 ; Machida, 2020 ; Rojas et al, 2022 ). In Table 1 HCV-associated HCC are involved in alterations of lncRNAs [( Hou and Bonkovsky, 2013 ; Lange et al, 2013 ; Zhang et al, 2015 ; Zhang et al, 2016 ; Fu et al, 2016 ; Shi et al, 2016 ; Hai et al, 2017 ; Wong et al, 2018 ; Sur et al, 2018 ; Toraih et al, 2018 ; Wang et al, 2018 ; Zhang et al, 2018 ; Cheng et al, 2019 ; Refai et al, 2019 ; Wang et al, 2019 ; Wu et al, 2019 ; Yang et al, 2019 ; Zhao et al, 2019 ; Zheng et al, 2019 ; Zhong et al, 2019 ; El-Khazragy et al, 2020 ; Ferrasi et al, 2020 ; Lorini et al, 2020 ; Machida, 2020 ; Mohyeldeen et al, 2020 ; Morishita et al, 2020 ; Oura et al, 2020 ; Unfried and Fortes, 2020 ; Jing et al, 2021 ; Sabry et al, 2021 ; Wong and Wong, 2021 ; Yao et al, 2021 ; Wang et al, 2022 ; Wei et al, 2022 )]. Upregulated lncRNAs include NORAD (LINC00657), HCP5, lnc-HOTAIR (HOX antisense intergenic RNA), CASC11, HEIM, eosinophil granule ontogeny transcript (EGOT), lncRNA SEMA3B-AS1 [SEMA3B Antisense RNA 1 (Head To Head)], TPT-1S, LINC01189.…”

Section: Migration/invasion/metastasismentioning

confidence: 99%

HCV and tumor-initiating stem-like cells

Machida

2022

Front. Physiol.

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Neoplasms contain tumor-initiating stem-like cells (TICs) that are characterized by increased drug resistance. The incidence of many cancer types have trended downward except for few cancer types, including hepatocellular carcinoma (HCC). Therefore mechanism of HCC development and therapy resistance needs to be understood. These multiple hits by hepatitis C virus (HCV) eventually promotes transformation and TIC genesis, leading to HCC development. This review article describes links between HCV-associated HCC and TICs. This review discusses 1) how HCV promotes genesis of TICs and HCC development; 2) how this process avails itself as a novel therapeutic target for HCC treatment; and 3) ten hall marks of TIC oncogenesis and HCC development as targets for novel therapeutic modalities.

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lncRNA HAND2‐AS1 overexpression inhibits cancer cell proliferation in hepatocellular carcinoma by downregulating RUNX2 expression

Cited by 17 publications

References 16 publications

Integrated analysis of multiple transcriptomic data identifies ST8SIA6‑AS1 and LINC01093 as potential biomarkers in HBV‑associated liver cancer

Integrated analysis of multiple transcriptomic data identifies ST8SIA6‑AS1 and LINC01093 as potential biomarkers in HBV‑associated liver cancer

Distinct HAND2/HAND2-AS1 Expression Levels Finetune Mesenchymal and Epithelial Cell Plasticity in Human Mesenchymal Stem Cells

HCV and tumor-initiating stem-like cells

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