Long non-coding RNAs (lncRNAs) in hepatocellular carcinoma progression: Biological functions and new therapeutic targets

Hashemi, Mehrdad; Mirzaei, Sepideh; Zandieh, Mohammad Arad; Rezaei, Sahar; Kakavand, Amirabbas; Dehghanpour, Amir; Esmaeili, Negin; Ghahremanzade, Azin; Saebfar, Hamidreza; Heidari, Hajar; Salimimoghadam, Shokooh; Taheriazam, Afshin; Entezari, Maliheh; Ahn, Kwang Seok

doi:10.1016/j.pbiomolbio.2022.12.004

Cited by 8 publications

(3 citation statements)

References 315 publications

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“…They are also involved in the complex regulatory network of cancer development and regulate different types of PCD [52][53][54]. Furthermore, there is growing evidence supporting the function of lncRNAs as key regulators of HCC [55,56], and potential diagnostic and prognostic markers of HCC [57]. Therefore, further elucidation of the role of lncRNAs in HCC could contribute to the current understanding of HCC progression and also to the determination of patient prognosis and selection of clinical treatment strategies.…”

Section: Discussionmentioning

confidence: 99%

A novel PANoptosis-related long non-coding RNA index to predict prognosis, immune microenvironment and personalised treatment in hepatocellular carcinoma

Wang,

Wan,

2024

Aging

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Background: PANoptosis is involved in the interaction of apoptosis, necroptosis and pyroptosis, playing a role in programmed cell death. Moreover, long non-coding RNAs (lncRNAs) regulate the PCD. This work aims to explore the role of PANoptosis-associated lncRNAs in hepatocellular carcinoma (HCC). Methods: Co-expression analysis identified PANoptosis-associated lncRNAs in HCC. Cox and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms were utilised to filter lncRNAs and establish a PANoptosis-related lncRNA index (PANRI). Additionally, Cox, Kaplan–Meier and receiver operating characteristic (ROC) curves were utilised to systematically evaluate the PANRI. Furthermore, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE), single sample gene set enrichment analysis (ssGSEA) and immune checkpoints were performed to analyse the potential of the PANRI in differentiating different tumour immune microenvironment (TIME) populations. The consensus clustering algorithm was used to distinguish individuals with HCC having different TIME subtypes. Finally, HCC cell lines HepG2 were utilised for further validation in in vitro experiments. Results: The PANRI differentiates patients according to risk. Notably, ESTIMATE and ssGSEA algorithms revealed a high immune infiltration status in high-risk patients. Additionally, consensus clustering divided the patients into three clusters to identify different subtypes of TIME. Moreover, i n vitro results showed that siRNA-mediated silencing of AL049840.4 inhibited the viability and migration of HepG2 cells and promoted apoptosis. Conclusions: This is the first PANoptosis-related, lncRNA-based risk index in HCC to assess patient prognosis, TIME and response to immunotherapy. This study offers novel perspectives on the role of PANoptosis-associated lncRNAs in HCC.

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Section: Discussionmentioning

confidence: 99%

A novel PANoptosis-related long non-coding RNA index to predict prognosis, immune microenvironment and personalised treatment in hepatocellular carcinoma

Wang,

Wan,

2024

Aging

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“…Various anticancer therapies have been employed in this regard. Multiple investigations have been undertaken to investigate the development of treatment resistance in HCC (197)(198)(199)(200). Zhang and colleagues (201) discovered that the prevention of miR-15a-5p in HCC leads to resistance to therapy due to the enhanced expression of elF4E.…”

Section: Lncrnas In the Regulation Of Drug Resistance In Hccmentioning

confidence: 99%

Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis

Tian,

Zhang,

Liu

et al. 2024

Front. Immunol.

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Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths in the world. The development and progression of HCC are closely correlated with the abnormal regulation of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Important biological pathways in cancer biology, such as cell proliferation, death, and metastasis, are impacted by these ncRNAs, which modulate gene expression. The abnormal expression of non-coding RNAs in HCC raises the possibility that they could be applied as new biomarkers for diagnosis, prognosis, and treatment targets. Furthermore, by controlling the expression of cancer-related genes, miRNAs can function as either tumor suppressors or oncogenes. On the other hand, lncRNAs play a role in the advancement of cancer by interacting with other molecules within the cell, which, in turn, affects processes such as chromatin remodeling, transcription, and post-transcriptional processes. The importance of ncRNA-driven regulatory systems in HCC is being highlighted by current research, which sheds light on tumor behavior and therapy response. This research highlights the great potential of ncRNAs to improve patient outcomes in this difficult disease landscape by augmenting the present methods of HCC care through the use of precision medicine approaches.

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“…lncRNAs are RNA molecules located in the cytoplasm, mitochondria, and nucleus, where they interact with specific proteins and mRNA, sponging and downregulating miRNA. Thus, lncRNAs mediate the apoptosis, proliferation, invasion, and metastasis of tumor cells, by modulating the activation/inhibition of cellular signaling pathways, or by interacting with the tumor microenvironment [ 101 ]. For example, DHRAS4-AS1 inhibits miR-522-3p and induces apoptosis via SOCS5 [ 102 ]; GSM3TV2 blocks miR-597 and stimulates growth and invasion by promoting FOSL2 expression [ 103 ]; FGD5-AS1 inhibits miR-873-5p, enhancing the expression of GTPBP4 [ 104 ], thereby favoring HCC progression by inhibiting miR-361-5p; SBF2-AS1 induces TGF-β1 signaling, resulting in growth and migration [ 104 , 105 ].…”

Section: Molecular Biology Of Hccmentioning

confidence: 99%

Molecular Mechanisms in Tumorigenesis of Hepatocellular Carcinoma and in Target Treatments—An Overview

Szilveszter,

Muntean,

Florea

2024

Biomolecules

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Hepatocellular carcinoma is the most common primary malignancy of the liver, with hepatocellular differentiation. It is ranked sixth among the most common cancers worldwide and is the third leading cause of cancer-related deaths. The most important etiological factors discussed here are viral infection (HBV, HCV), exposure to aflatoxin B1, metabolic syndrome, and obesity (as an independent factor). Directly or indirectly, they induce chromosomal aberrations, mutations, and epigenetic changes in specific genes involved in intracellular signaling pathways, responsible for synthesis of growth factors, cell proliferation, differentiation, survival, the metastasis process (including the epithelial–mesenchymal transition and the expression of adhesion molecules), and angiogenesis. All these disrupted molecular mechanisms contribute to hepatocarcinogenesis. Furthermore, equally important is the interaction between tumor cells and the components of the tumor microenvironment: inflammatory cells and macrophages—predominantly with a pro-tumoral role—hepatic stellate cells, tumor-associated fibroblasts, cancer stem cells, extracellular vesicles, and the extracellular matrix. In this paper, we reviewed the molecular biology of hepatocellular carcinoma and the intricate mechanisms involved in hepatocarcinogenesis, and we highlighted how certain signaling pathways can be pharmacologically influenced at various levels with specific molecules. Additionally, we mentioned several examples of recent clinical trials and briefly described the current treatment protocol according to the NCCN guidelines.

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Long non-coding RNAs (lncRNAs) in hepatocellular carcinoma progression: Biological functions and new therapeutic targets

Cited by 8 publications

References 315 publications

A novel PANoptosis-related long non-coding RNA index to predict prognosis, immune microenvironment and personalised treatment in hepatocellular carcinoma

A novel PANoptosis-related long non-coding RNA index to predict prognosis, immune microenvironment and personalised treatment in hepatocellular carcinoma

Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis

Molecular Mechanisms in Tumorigenesis of Hepatocellular Carcinoma and in Target Treatments—An Overview

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