Long non-coding RNA OIP5-AS1 promotes pancreatic cancer cell growth through sponging miR-342-3p via AKT/ERK signaling pathway

Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a long non-coding RNA (lncRNA), has been reported to link with the progression of some cancers. However, its biological functions and underlying molecular mechanisms in pancreatic cancer are largely unknown. The aim of this study was to investigate the role of lncRNA OIP5-AS1 in pancreatic cancer. Quantitative real-time PCR analysis revealed that OIP5-AS1 is highly expressed in pancreatic cancer tissues versus adjacent non-tumor tissues. In vitro functional assays showed that downregulation of OIP5-AS1 or overexpression of miR-342-3p inhibited the proliferation, decreased Ki67 expression, and induced cell cycle arrest in pancreatic cancer cells. The expression of cyclinD1, CDK4, and CDK6 was decreased by knockdown of OIP5-AS1. Moreover, we found that OIP5-AS1 acted as a miR-342-3p sponge to suppress its expression and function. Dual-luciferase assay confirmed the interaction of OIP5-AS1 and miR-342-3p and verified anterior gradient 2 (AGR2) as a direct target of miR-342-3p. Results showed that depletion of miR-342-3p abolished the inhibitory effects of OIP5-AS1 knockdown on pancreatic cancer cell growth. The expression of Ki67, AGR2, cyclinD1, CDK4, CDK6, p-AKT, and p-ERK1/2 was reversed by silencing of miR-342-3p in pancreatic cancer cells with OIP5-AS1 knockdown. Further, knockdown of OIP5-AS1 suppressed tumor growth in a xenograft mouse model of pancreatic cancer. OIP5-AS1 induced pancreatic cancer progression via activation of AKT and ERK signaling pathways. Therefore, we demonstrate that OIP5-AS1 functions as oncogene in pancreatic cancer and its downregulation inhibits pancreatic cancer growth by sponging miR-342-3p via targeting AGR2 through inhibiting AKT/ERK signaling pathway.

     

Long noncoding RNA OIP5-AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR signaling pathway by sponging the miR-340-5p

The abnormal expression of long noncoding RNAs (lncRNAs) plays an important role in the regulation of human cancer progression and drug resistance. The lncRNA OPI5-AS1 is a crucial regulator in some cancers; however, its role in cisplatin resistance of osteosarcoma remains unclear. We found that OIP5-AS1 was significantly upregulated in cisplatin-resistant (CR) osteosarcoma cells MG63-CR and SaOS2-CR compared with the corresponding parental cells. OIP5-AS1 silencing suppressed cell growth in vitro and in vivo, and promoted apoptosis of MG63-CR and SaOS2-CR cells, indicating that knockdown of OIP5-AS1 significantly decreased cisplatin resistance in MG63-CR and SaOS2-CR cells. This conclusion was supported by the decreased expression of the drug resistance-related factors multidrug resistance-associated protein 1 (MRP1) and P-glycoprotein (P-gp) upon OIP5-AS1 silencing. In addition, OIP5-AS1 downregulation suppressed the PI3K/AKT/mTOR signaling pathway. Importantly, we demonstrated that OIP5-AS1 functions as a competing endogenous RNA of miR-340-5p and regulates the expression of lysophosphatidic acid acyltransferase (LPAATβ), which is a target of miR-340-5p. Moreover, downregulation of miR-340-5p partly reversed the inhibitory effect of OIP5-AS1 knockdown on the PI3K/AKT/mTOR pathway and therefore counteracted cisplatin resistance in MG63-CR and SaOS2-CR cells. In conclusion, OIP5-AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR signaling pathway by sponging the miR-340-5p. Our results contribute to a better understanding of the function and mechanism of OIP5-AS1 in osteosarcoma cisplatin resistance.     

Long noncoding RNA OIP5-AS1 aggravates cell proliferation,migration in gastric cancer by epigenetically silencing NLRP6 expression via binding EZH2

The critical role of long noncoding RNAs (lncRNAs) in the development of multiple cancers has been revealed either functioning as a tumor initiator or a cancer suppressor. A widely recognized OIP5 antisense RNA 1 (lncRNA OIP5-AS1) has been validated to be an essential regulator of the tumorigenesis of various malignancies. Whereas, the potential role and the exact mechanism of lncRNA OIP5-AS1 by which OIP5-AS1 mediates gastric cancer (GC) progression remains vague. Therefore, first our work probed its expression levels in GC cell lines and related normal cells by real-time quantitative polymerase chain reaction. The heightened level of OIP5-AS1 was detected in GC cell lines. In terms of its cellular effects, we performed a series of functional experiments and as presented in the assays, the proliferative potential and motility was diminished. However, more apoptotic cells were induced with the introduction of OIP5-AS1 silencing. Meanwhile, higher Nod-like receptor pyrin domain-containing protein 6 (NLRP6) and enhancer of zeste homolog 2 (EZH2) expression in the GC cells was monitored. Besides, OIP5-AS1 was disclosed to locate mainly in the nucleus. In terms of mechanism, OIP5-AS1 directly bound to EZH2 and obstructed NLRP6 expression, speeding up GC progression.     

Long noncoding RNA STXBP5-AS1 inhibits cell proliferation,migration, and invasion via preventing the PI3K/AKT against STXBP5 expression in non–small-cell lung carcinoma

Long noncoding RNAs participate in carcinogenesis and tumor progression in non–small-cell lung carcinoma (NSCLC), but the mechanisms underlying NSCLC tumorigenesis remain to be fully elucidated. Here, we reported the functional role and potential mechanism of long noncoding RNA syntaxin-binding protein 5-antisense RNA 1 (STXBP5-AS1) in NSCLC. First, our data revealed that the expression levels of STXBP5-AS1 in 31 NSCLC tissues were lower than in adjacent tissues using quantitative polymerase chain reaction (qPCR) and its expression was significantly associated with tumor metastasis of NSCLC patients. Moreover, CCK-8, scratch wound healing and transwell assay suggested that upregulation of STXBP5-AS1 repressed the proliferation, migration, and invasion in A549, NCI-H292, and NCI-H460 cells. To explore the potential mechanism of STXBP5-AS1 in NSCLC, we first investigated the relationship among STXBP5-AS1, STXBP5, and AKT1 in A549 cells. Results indicated that STXBP5-AS1 was negatively related with STXBP5 and AKT1 at messenger RNA expression level using qPCR. In addition, we observed that STXBP5-AS1 had reverse effects on the protein levels of STXBP5 and phosphorylated AKT1 (p-AKT1) in A549 cells via Western blot assay, despite no significant effects on AKT1. Subsequently, LY294002, as the phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway inhibitor, was used to further confirm the regulatory mechanism of STXBP5-AS1, which showed that knockdown of STXBP5-AS1 could rescue the expression of STXBP5 and p-AKT1 protein expression levels in A549 cells. Taken together, our results suggested that STXBP5-AS1, as a tumor suppressor, inhibits cell proliferation, migration, and invasion by preventing the PI3K/AKT against STXBP5 expression in NSCLC.     

METTL14 promotes tumorigenesis by regulating lncRNA OIP5-AS1/miR-98/ADAMTS8 signaling in papillary thyroid cancer

BackgroundPapillary thyroid cancer (PTC) is the most common type of cancer of the endocrine system. Long noncoding RNAs (lncRNAs) are emerging as a novel class of gene expression regulators associated with tumorigenesis. Through preexisting databases available for differentially expressed lncRNAs in PTC, we uncovered that lncRNA OIP5-AS1 was significantly upregulated in PTC tissues. However, the function and the underlying mechanism of OIP5-AS1 in PTC are poorly understood.MethodsExpression of lncRNA OIP5-AS1 and miR-98 in PTC tissue and cells were measured by quantitative real-time PCR (qRT-PCR). And expression of METTL14 and ADAMTS8 in PTC tissue and cells were measured by qRT-PCR and western blot. The biological functions of METTL14, OIP5-AS1, and ADAMTS8 were examined using MTT, colony formation, transwell, and wound healing assays in PTC cells. The relationship between METTL14 and OIP5-AS1 were evaluated using RNA immunoprecipitation (RIP) and RNA pull down assay. And the relationship between miR-98 and ADAMTS8 were examined by luciferase reporter assay. For in vivo experiments, a xenograft model was used to investigate the effects of OIP5-AS1 and ADAMTS8 in PTC.ResultsFunctional validation revealed that OIP5-AS1 overexpression promotes PTC cell proliferation, migration/invasion in vitro and in vivo, while OIP5-AS1 knockdown shows an opposite effect. Mechanistically, OIP5-AS1 acts as a target of miR-98, which activates ADAMTS8. OIP5-AS1 promotes PTC cell progression through miR-98/ADAMTS8 and EGFR, MEK/ERK pathways. Furthermore, RIP and RNA pull down assays identified OIP5-AS1 as the downstream target of METTL14. Overexpression of METTL14 suppresses PTC cell proliferation and migration/invasion through inhibiting OIP5-AS1 expression and regulating EGFR, MEK/ERK pathways.ConclusionsCollectively, our findings demonstrate that OIP5-AS1 is a METTL14-regulated lncRNA that plays an important role in PTC progression and offers new insights into the regulatory mechanisms underlying PTC development.Subject terms: Tumour biomarkers, Oncogenes     

LncRNA OIP5-AS1 facilitates ox-LDL-induced endothelial cell injury through the miR-98-5p/HMGB1 axis

Cerebrovascular diseases have a high mortality and disability rate in developed countries. Endothelial cell injury is the main cause of atherosclerosis and cerebrovascular disease. Long non-coding RNA (lncRNA) has been proved to participate in the progression of endothelial cell. Our study aimed to develop the function of lncRNA opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in oxidative low-density lipoprotein (ox-LDL)-induced endothelial cell injury. The expression of OIP5-AS1, miR-98-5p and High-mobility group protein box-1 (HMGB1) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry were used to detect the cell proliferation and apoptosis. The levels of cyclinD1, Bcl-2 Associated X Protein (Bax), Cleaved-caspase-3, Toll like receptors 4 (TLR4), phosphorylation of p65 (p-P65), phosphorylation of nuclear factor-kappa B inhibitor α (p-IκB-α) and HMGB1 were measured by Western blot. The concentrations of Interleukin-6 (IL-6), Interleukin-1β (IL-1β) and Tumor necrosis factor-α (TNF-α) were detected by Enzyme-linked immunosorbent assay (ELISA). The production of Reactive oxygen species (ROS), Superoxide Dismutase (SOD) and malondialdehyde (MDA) was detected by the corresponding kit. The targets of OIP5-AS and miR-98-5p were predicted by starBase 3.0 and TargetScan and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The expression of OIP5-AS1 was upregulated, while miR-98-5p was downregulated in ox-LDL-induced human umbilical vein endothelial cells (HUVECs). Functionally, knockdown of OIP5-AS1 induced proliferation and inhibited apoptosis, inflammatory injury and oxidative stress injury in ox-LDL-induced HUVEC cells. Interestingly, miR-98-5p was a target of OIP5-AS1 and miR-98-5p inhibition abolished the effects of OIP5-AS1 downregulation on ox-LDL-induced HUVECs injury. More importantly, miR-98-5p directly targeted HMGB1, and OIP5-AS1 regulated the expression of HMGB1 by sponging miR-98-5p. Finally, OIP5-AS1 regulated the TLR4/nuclear factor-kappa B (NF-κB) signaling pathway through miR-98-5p/HMGB1 axis. LncRNA OIP5-AS1 accelerates ox-LDL-induced endothelial cell injury through regulating HMGB1 mediated by miR-98-5p via the TLR4/NF-κB signaling pathway.

     

MNX1-AS1 is a novel biomarker for predicting clinical progression and poor prognosis in lung adenocarcinoma

Motor neuron and pancreas homeobox 1-antisense RNA1 (MNX1-AS1) is a novel long noncoding RNA and has been suggested to be overexpressed in human ovarian cancer and glioma. The role of MNX1-AS1 in lung cancer was still unknown. In our study, we observed levels of MNX1-AS1 expression through analyzing The Cancer Genome Atlas and found MNX1-AS1 expression was highly expressed in lung adenocarcinoma tissues compared with normal lung tissues, but there was no statistical difference between lung squamous cell carcinoma tissues and normal lung tissues. Furthermore, we conducted quantitative real-time polymerase chain reaction, and confirmed that the expression of MNX1-AS1 was definitely higher in lung adenocarcinoma tissue samples, but not in lung squamous cell carcinoma tissue samples. In addition, high MNX1-AS1 expression was found to be associated with the low differentiated degree, advanced clinical stage, big tumor size, lymph node metastasis, and distant metastasis in lung adenocarcinoma patients. High expression of MNX1-AS1 was negatively correlated with overall survival time and served as an independent unfavorable prognostic factor in patients with lung adenocarcinoma. The in vitro functional studies suggested that suppression of MNX1-AS1 inhibited lung adenocarcinoma cell proliferation and migration, and promoted apoptosis. In conclusion, MNX1-AS1 is overexpressed in lung adenocarcinoma, and associated with clinical progression and poor prognosis.     

Long noncoding RNA OIP5-AS1 acts as a competing endogenous RNA to promote glutamine catabolism and malignant melanoma growth by sponging miR-217

The long noncoding RNA (lncRNA) OIP5-AS1 has been considered to promote the growth and metastasis of many human tumors. However, the role of OIP5-AS1 in melanoma has not been reported. In this study, we found that OIP5-AS1 levels were significantly elevated in melanoma tissue and that high OIP5-AS1 expression was an independent risk factor for the poor survival of patients with melanoma. miR-217 suppressed glutamine catabolism in melanoma cells by targeting glutaminase (GLS), the rate-limiting enzyme of glutamine catabolism. We also demonstrated that OIP5-AS1 acted as a sponge of miR-217 to upregulate GLS expression, thus promoting glutamine catabolism and melanoma growth. Overall, this result elucidates a new mechanism for OIP5-AS1 in metabolism in melanoma and provides a potential therapeutic target for patients with melanoma.     

Transient receptor potential melastatin 2–antisense RNA is overexpresed in osteosarcoma and regulates cell proliferation and apoptosis

Accumulating evidence suggested that transient receptor potential melastatin 2–antisense RNA (TRPM2-AS) played crucial roles in the progression of human cancers. However, the role of TRPM2-AS was still unknown in osteosarcoma. The aim of this study was to explore the clinical significance of TRPM2-AS in osteosarcoma patients, and determine the role of TRPM2-AS on osteosarcoma cell proliferation and apoptosis. In our results, we identified a novel oncogenic long noncoding RNA TRPM2-AS, which was overexpressed in osteosarcoma tissues and cells, and correlated with advanced Enneking stage, large tumor size and high histological grade in osteosarcoma cases. Survival analysis indicated that osteosarcoma patients with high TRPM2-AS expression had an obviously shorter overall survival time than those with low TRPM2-AS expression. Loss-of-function studies suggested that suppression of TRPM2-AS expression inhibited osteosarcoma cell proliferation and induced cell apoptosis through upregulating cleaved caspase-3 and cleaved caspase-9 expression. In conclusion, TRPM2-AS acts as an oncogenic long noncoding RNA and predicts poor prognosis in osteosarcoma.     

The role of lncRNA OIP5-AS1 in cancer development and progression

OIP5-AS1, a conserved lncRNA, has been reported to be involved in several biological and pathological processes, including oncogenesis. OIP5-AS1 exerts its oncogenic or antitumor functions via regulation of different miRNAs in various cancer types. In this review, we describe the dysregulation of OIP5-AS1 expression in a variety of human cancers. Moreover, we discuss the multiple functions of OIP5-AS1 in cancer, including in proliferation, apoptosis, autophagy, ferroptosis, cell cycle, migration, metastasis, invasion, epithelial to mesenchymal transition, angiogenesis, cancer stem cells and drug resistance. Furthermore, we provide a future perspective for OIP5-AS1 research. We conclude that targeting OIP5-AS1 might be a promising cancer therapy approach.

     

Long non-coding RNA FEZF1-AS1 induced progression of ovarian cancer via regulating miR-130a-5p/SOX4 axis

Emerging studies have revealed the critical role of long non-coding RNAs (lncRNAs) in epithelial ovarian cancer (EOC) development and progression. Till now, the roles and potential mechanisms regarding FEZF1 antisense RNA 1 (FEZF1-AS1) within ovarian cancer (OC) remain unclear. The objective of this study was to uncover the biological function and the underlying mechanism of LncRNA FEZF1-AS1 in OC progression. FEZF1-AS1 expression levels were studied in cell lines and tissues of human ovarian cancer. In vitro studies were performed to evaluate the impact of FEZF1-AS1 knock-down on the proliferation, invasion, migration and apoptosis of OC cells. Interactions of FEZF1-AS1 and its target genes were identified by luciferase reporter assays. Our data showed overexpression of FEZF1-AS1 in OC cell lines and tissues. Cell migration, proliferation, invasion, wound healing and colony formation were suppressed by silencing of FEZF1-AS1. In contrast, cell apoptosis was promoted by FEZF1-AS1 knock-down in vitro. Furthermore, online bioinformatics analysis and tools suggested that FEZF1-AS1 directly bound to miR-130a-5p and suppressed its expression. Moreover, the inhibitory effects of miR-130a-5p on the OC cell growth were reversed by FEZF1-AS1 overexpression, which was associated with the increase in SOX4 expression. In conclusion, our results revealed that FEZF1-AS1 promoted the metastasis and proliferation of OC cells by targeting miR-130a-5p and its downstream SOX4 expression.     

LncRNA TP73-AS1 predicts poor prognosis and functions as oncogenic lncRNA in osteosarcoma

TP73 antisense RNA 1 (TP73-AS1), a novel long noncoding RNA (lncRNA), has been suggested to be deregulated in various human cancers and serve as a tumor suppressor or promoter, depending on tumor types. The role of TP73-AS1 in osteosarcoma is still unknown. In our results, TP73-AS1 was highly expressed in osteosarcoma tissue samples and cell lines compared with matching adjacent nontumor tissue specimens and a normal human osteoblast cell line, respectively. Moreover, high expression of TP73-AS1 was statistically associated with advanced Enneking stage, large tumor size, present distant metastasis, and poor histological grade, while exhibiting no statistical association with age, sex, and tumor site. The survival analyses showed that patients with osteosarcoma with high expression of TP73-AS1 obviously had lower overall survival than osteosarcoma patients with low expression of TP73-AS1, and high expression of TP73-AS1 was an independent poor prognostic factor for osteosarcoma patients. The experiments in vitro indicated that inhibition of TP73-AS1 expression depressed osteosarcoma cell viability, migration, and invasion, and arrested cell cycle. In conclusion, TP73-AS1 serves as oncogenic lncRNA participated in osteosarcoma progression.     

LncRNA OIP5-AS1 regulates radioresistance by targeting DYRK1A through miR-369-3p in colorectal cancer cells

Object

This study aimed to investigate the role of lncRNA OIP5-AS1 in regulating radioresistance of colorectal cancer (CRC) cells.

SUMOylation of IGF2BP2 promotes vasculogenic mimicry of glioma via regulating OIP5-AS1/miR-495-3p axis

Rationale: Glioma is the most common primary malignant tumor of human central nervous system, and its rich vascular characteristics make anti-angiogenic therapy become a therapeutic hotspot. However, the existence of glioma VM makes the anti-angiogenic therapy ineffective. SUMOylation is a post-translational modification that affects cell tumorigenicity by regulating the expression and activity of substrate proteins.Methods: The binding and modification of IGF2BP2 and SUMO1 were identified using Ni²⁺-NTA agarose bead pull-down assays, CO-IP and western blot; and in vitro SUMOylation assays combined with immunoprecipitation and immunofluorescence staining were performed to explore the detail affects and regulations of the SUMOylation on IGF2BP2. RT-PCR and western blot were used to detect the expression levels of IGF2BP2, OIP5-AS1, and miR-495-3p in glioma tissues and cell lines. CCK-8 assays, cell transwell assays, and three-dimensional cell culture methods were used for evaluating the function of IGF2BP2, OIP5-AS1, miR-495-3p, HIF1A and MMP14 in biological behaviors of glioma cells. Meantime, RIP and luciferase reporter assays were used for inquiring into the interactions among IGF2BP2, OIP5-AS1, miR-495-3p, HIF1A and MMP14. Eventually, the tumor xenografts in nude mice further as certained the effects of IGF2BP2 SUMOylation on glioma cells.Results: This study proved that IGF2BP2 mainly binds to SUMO1 and was SUMOylated at the lysine residues K497, K505 and K509 sites, which can be reduced by SENP1. SUMOylation increased IGF2BP2 protein expression and blocked its degradation through ubiquitin-proteasome pathway, thereby increasing its stability. The expressions of IGF2BP2 and OIP5-AS1 were up-regulated and the expression of miR-495-3p was down-regulated in both glioma tissues and cells. IGF2BP2 enhances the stability of OIP5-AS1, thereby increasing the binding of OIP5-AS1 to miR-495-3p, weakening the binding of miR-495-3p to the 3''UTR of HIF1A and MMP14 mRNA, and ultimately promoting the formation of VM in glioma.Conclusions: This study first revealed that SUMOylation of IGF2BP2 regulated OIP5-AS1/miR-495-3p axis to promote VM formation in glioma cells and xenografts growth in nude mice, providing a new idea for molecular targeted therapy of glioma.     

Long noncoding RNA FLVCR1-AS1 aggravates biological behaviors of glioma cells via targeting miR-4731-5p/E2F2 axis

Long noncoding RNAs (lncRNAs) display essential roles in cancer progression. FLVCR1-AS1 is a rarely investigated lncRNAs involved in various human cancers, such as hepatocellular carcinoma and lung cancer. However, its function in glioma has not been clarified. In our study, we found that FLVCR1-AS1 was highly expressed in glioma tissues and cell lines. And upregulation of FLVCR1-AS1 predicted poor prognosis in patients with glioma. Moreover, FLVCR1-AS1 knockdown inhibited proliferation, migration and invasion of glioma cells. Through bioinformatics analysis, we identified that FLVCR1-AS1 was a sponge for miR-4731-5p to upregulate E2F2 expression. Moreover, rescue assays indicated that FLVCR1-AS1 modulated E2F2 expression to participate in glioma progression. Altogether, our research demonstrates that the FLVCR1-AS1/miR-4731-5p/E2F2 axis is a novel signaling in glioma and may be a potential target for tumor therapy.     

Silencing of long noncoding RNA LEF1-AS1 prevents the progression of hepatocellular carcinoma via the crosstalk with microRNA-136-5p/WNK1

Long noncoding RNAs (lncRNAs) have been recognized as cancer-associated biological molecules, favoring hepatocellular carcinoma (HCC) progression. This study was conducted to elucidate the effects lncRNA lymphoid enhancer-binding Factor 1 antisense RNA (LEF1-AS1) on the pathological development of HCC, along with the crosstalk involving microRNA-136-5p (miR-136-5p) and with-no-K (lysine) kinase 1 (WNK1). The study recruited primary HCC tissues and their corresponding nonneoplastic liver tissues. The gain- and loss-of-function studies were performed in HCC cells HuH-7 and tumor xenografts in nude mice. The dual luciferase reporter gene assay system, RNA pull-down, and radioimmunoprecipitation assays were applied to detect their interactions among lncRNA LEF1-AS1, miR-136-5p, and WNK1. 5-Ethynyl-2′-deoxyuridine staining, scratch test, Transwell assays, and in vitro tube formation assays were conducted to examine HCC cell proliferation, migration, and invasion and HUVEC angiogenesis. HCC tissues and cells contained high lncRNA LEF1-AS1 expression. LncRNA LEF1-AS1 upregulation triggered markedly increased HCC cell proliferation, migration, and invasion and human umbilical vein endothelial cell angiogenesis. In vivo silencing lncRNA LEF1-AS1 resulted in reduced tumor cell vitality and matrix metalloproteinase-9 and the vascular endothelial growth factor expression. Additionally, the role of lncRNA LEF1-AS1 was found to be largely dependent on WNK1. Association of lncRNA LEF1-AS1 with WNK1 blocked the inhibitory effect of miR-136-5p on WNK1, which was confirmed by in vivo experiments. Altogether, our results revealed an important role of lncRNA LEF1-AS1 in regulating the HCC progression by regulating WNK1, providing a potential biomarker for the therapeutic modalities regarding HCC.