lncRNA- RP11-156p1.3, novel diagnostic and therapeutic targeting via CRISPR/Cas9 editing in hepatocellular carcinoma

Ali, H.A.M.; Boshra, Mariam Sameh; Meteini, Mahmoud Shawky El; Shafei, Ayman; Matboli, Marwa

doi:10.1016/j.ygeno.2020.06.020

Cited by 28 publications

(17 citation statements)

References 36 publications

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“…Although recent studies have identified many novel HCC biomarkers, including lncRNAs [ 39 – 41 ], LncRNAs have been found to have functions in HCC development. Studies have indicated that the lncRNAs, MIAT [ 42 ], GABPB1 [ 43 ], and PDPK2P [ 44 ] influence tumor progression in HCC.…”

Section: Discussionmentioning

confidence: 99%

LncRNA PTPRG-AS1 Promotes the Metastasis of Hepatocellular Carcinoma by Enhancing YWHAG

Chen

Zhang

et al. 2021

Journal of Oncology

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Objectives. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. LncRNA PTPRG-AS1 (PTPRG-AS1) has been confirmed to function as a regulator in various cancers, whose function during HCC tumorigenesis is still not clear now. Thus, we aim to dig out the biological function and its mechanisms of PTPRG-AS1 in HCC. Methods. PTPRG-AS1 relative expression in tissues and cells was detected and analyzed using real-time quantitative PCR (qRT-PCR). Subcellular distribution of PTPRG-AS1 was examined by FISH experiments. The effects of PTPRG-AS1 in the growth of HCC were studied by in vitro CCK-8 experiments, transwell invasion experiments, and in vivo xenograft tumor experiments. Dual-Luciferase reporter assay was performed to verify the interaction between PTPRG-AS1 and miR-199a-3p or miR-199a-3p and its target gene, YWHAG. Results. PTPRG-AS1 was upregulated in HCC tissues compared with adjacent normal tissues. We identified PTPRG-AS1 mainly localized in the cytoplasm of HCC cells. Downregulation of PTPRG-AS1 suppressed HCC progression, while overexpression of PTPRG-AS1 showed the opposite effects. Furthermore, PTPRG-AS1 served as a miR-199a-3p sponge and positively regulated YWHAG expression. Besides, PTPRG-AS1 could promote HCC through miR-199a-3p/YWHAG axis. Conclusions. Taken together, we demonstrated PTPRG-AS1 may serve as a ceRNA and reversely regulates the expression of miR-199a-3p, thus facilitating HCC tumorigenesis and metastasis, which is expected to provide new clues for the treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

LncRNA PTPRG-AS1 Promotes the Metastasis of Hepatocellular Carcinoma by Enhancing YWHAG

Chen

Zhang

et al. 2021

Journal of Oncology

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“…In an orthotopic mouse model of BEL-7402 human HCC cells, this combination treatment showed a marked reduction in tumor growth compared to either agent alone without exerting any toxicity. Similar survivin-targeted strategy using lactose-derived branched-cationic biopolymer (LBP), with the rationale that lactose will bind to ASGPR providing targeted delivery, in BEL-7402 orthotopic model also showed marked tumor reduction without any toxic effect [ 86 ]. These studies demonstrate that specifically targeting survivin by CRISPR/Cas9 provides a safe and attractive strategy for HCC management with promising clinical translation.…”

Section: Gene Therapy Approaches For Hccmentioning

confidence: 99%

Emerging Therapies for Hepatocellular Carcinoma (HCC)

Chakraborty

Sarkar

2022

Cancers

176

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Hepatocellular carcinoma (HCC) arises from hepatocytes and accounts for 90% of primary liver cancer. According to Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN) 2020, globally HCC is the sixth most common cancer and the third most common cause of cancer-related deaths. Reasons for HCC prognosis remaining dismal are that HCC is asymptomatic in its early stages, leading to late diagnosis, and it is markedly resistant to conventional chemo- and radiotherapy. Liver transplantation is the treatment of choice in early stages, while surgical resection, radiofrequency ablation (RFA) and trans arterial chemoembolization (TACE) are Food and Drug Administration (FDA)-approved treatments for advanced HCC. Additional first line therapy for advanced HCC includes broad-spectrum tyrosine kinase inhibitors (TKIs), such as sorafenib and lenvatinib, as well as a combination of immunotherapy and anti-angiogenesis therapy, namely atezolizumab and bevacizumab. However, these strategies provide nominal extension in the survival curve, cause broad spectrum toxic side effects, and patients eventually develop therapy resistance. Some common mutations in HCC, such as in telomerase reverse transcriptase (TERT), catenin beta 1 (CTNNB1) and tumor protein p53 (TP53) genes, are still considered to be undruggable. In this context, identification of appropriate gene targets and specific gene delivery approaches create the potential of gene- and immune-based therapies for the safe and effective treatment of HCC. This review elaborates on the current status of HCC treatment by focusing on potential gene targets and advanced techniques, such as oncolytic viral vectors, nanoparticles, chimeric antigen receptor (CAR)-T cells, immunotherapy, and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9), and describes future prospects in HCC treatment.

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“…Functional analysis of this lncRNA was demonstrated by the use of CRISPR cas9 knock-out in HepG2 cells, which showed that the level of the genetic network was reversed and the protein levels of TNF α and NFκβ were decreased, together with a significant decrease in cell count and viability. It indicated that lnc-RNA RP11-156p1.3 can be a promising therapeutic target as well as a diagnostic tool [121].…”

Section: Exosome-derived Lncrnasmentioning

confidence: 99%

Circulating Long and Circular Noncoding RNA as Non-Invasive Diagnostic Tools of Hepatocellular Carcinoma

et al. 2021

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Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide, partially due to late diagnosis of the disease. Growing evidence in the field of biomarker discovery has shown the promising use of nucleic acid in the early detection of many cancers, including HCC. Here, we review data on how various long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) could be used as a diagnostic tool for HCC being differentially expressed in HCC compared to non-HCC patients. These non-coding RNAs (ncRNAs) showed high stability in the blood being present as free-circulating molecules or encapsulated into exosomes. This review reports some recent evidence on the use of lncRNAs and circRNAs as possible diagnostic biomarkers for HCC. Further, their pathophysiological mechanism in liver carcinogenesis was also described, elucidating the complex regulatory networks making these ncRNAs of particular relevance for the study of liver malignancy cancer.

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lncRNA- RP11-156p1.3, novel diagnostic and therapeutic targeting via CRISPR/Cas9 editing in hepatocellular carcinoma

Cited by 28 publications

References 36 publications

LncRNA PTPRG-AS1 Promotes the Metastasis of Hepatocellular Carcinoma by Enhancing YWHAG

LncRNA PTPRG-AS1 Promotes the Metastasis of Hepatocellular Carcinoma by Enhancing YWHAG

Emerging Therapies for Hepatocellular Carcinoma (HCC)

Circulating Long and Circular Noncoding RNA as Non-Invasive Diagnostic Tools of Hepatocellular Carcinoma

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