HEIH Expression Research Articles

Expression and Clinical Significance of LncRNA HEIH in Patients with Acute Myeloid Leukemia

To investigate the expression and clinical significance of long noncoding RNA(lncRNA) HEIH in patients with acute myeloid leukemia (AML). 50 newly diagnosed AML patients (except M3) admitted to the First Affiliated Hospital of Bengbu Medical College from January 2019 to December 2020 were included in the study, with 30 patients with non-hematological malignancies as controls. The relative expression level of lncRNA HEIH in all patients were detected, the correlation of clinical characteristics, gene mutations, FAB classification, efficacy, prognosis and overall survival (OS) of AML patients with the expression level of lncRNA HEIH were analyzed. The expression level of lncRNA HEIH in AML patients was significantly higher than that in patients with non-hematological malignancies (P <0.01). Moreover, AML patients with high white blood cell count (WBC), CEBPA and FLT3 mutations, poor efficacy, and poor prognosis often showed higher expression of lncRNA HEIH, and patients with high lncRNA HEIH expression showed a shorter overall survival (OS). lncRNA HEIH shows an unique molecular biological significance in AML patients, which may provide a new approach for diagnosis, monitoring and targeted therapy of AML.

LncRNA HEIH/miR-4500/IGF2BP1/c-Myc Feedback Loop Accelerates Bladder Cancer Cell Growth and Stemness.

Bladder cancer (BCa) is one of the most prevalent malignancies and more common in men. An aberrantly expressed long noncoding RNA (lncRNA) hepatocellular carcinoma up-regulated EZH2-associated lncRNA (HEIH) has been reported to be implicated in the progression of many cancers, but its role in BCa remains little known. Our study intended to uncover whether and how HEIH regulates BCa progression. Quantitative real-time polymerase chain reaction (RT-qPCR) was adopted to determine HEIH expression in BCa cell lines. Functional experiments were performed to examine the effects of HEIH on BCa cell proliferation, apoptosis, migration, invasion and stemness. Bioinformatics analysis and mechanism experiments were conducted to investigate the regulatory relationship between HEIH and related molecules in BCa. HEIH expression was observed to be significantly increased in BCa cell lines. HEIH depletion significantly hindered BCa cell proliferation, migration and invasion. Besides, HEIH up-regulated MYC proto-oncogene, and bHLH transcription factor (c-Myc) expression to promote BCa cell stemness. Moreover, HEIH served as a sponge for miR-4500 to modulate insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) expression, thereby stabilizing c-Myc mRNA level. Our study demonstrated a positive feedback loop of HEIH/miR-4500/IGF2BP1/c-Myc in BCa progression, offering a novel insight into a possible BCa therapy.

Identification and verification of YBX3 and its regulatory gene HEIH as an oncogenic system: A multidimensional analysis in colon cancer.

The novel gene YBX3 is important for regulating translation and RNA catabolism and encodes a protein with a highly conserved cold-shock domain. However, its pathogenic roles across cancers (e.g., colon cancer) and its regulation remain unclear. We identified the pathogenic roles of YBX3 and its regulatory lncRNA HEIH in various cancers and investigated their effects on tumor progression in colon cancer. Methods including RNA pull-down, MS, and TMA of 93 patients, qPCR of 12 patients with diverse clinicopathologic stages, and western blotting were performed. The pancancer analysis showed that YBX3 expression varies significantly among not only cancer types but also molecular and immune subtypes of the same cancer. Furthermore, its expression in colon cancer is clinically significant, and there is an obvious negative regulatory association between HEIH and YBX3. Among various cancers, especially colon cancer, YBX3 is more related than HEIH expression to the clinical features and prognosis of subgroups. The receiver operating characteristic analysis showed that HEIH and YBX3 have similar predictive capacity in various cancers. The analysis of differentially expressed genes in colon cancer revealed that they have similar hub gene networks, indicating an oncogenic system with a strong overlap. The results also suggest that YBX3 is associated with tumor immune evasion via different mechanisms involving T-cell exclusion in different cancer types and by the tumor infiltration of immune cells. Interestingly, scRNA-seq revealed that HEIH inhibits this phenomenon. Our results also suggest that YBX3 expression is associated with immune or chemotherapeutic outcomes in various cancers, and YBX3 exhibited a higher predictive power than two of seven standardized biomarkers for response outcomes and overall survival of immune checkpoint blockade subcohorts. In colon cancer cell lines, lncRNA-HEIH and YBX3 associate. MS confirmed that YBX3 was pulled down with HEIH, and western blot showed that HEIH knockdown disinhibited YBX3. This study strongly suggests that lncRNA-HEIH/YBX3 is a pancancer immune-oncogenic system and could serve as a biomarker for diagnosis and prognosis and as a therapeutic target, especially in colon cancer.

HEIH Promotes Malignant Progression of Gastric Cancer by Regulating STAT3-Mediated Autophagy and Glycolysis.

To study the clinical value of HEIH hyperexpression in gastric cancer and the molecular mechanism of promoting malignant proliferation of gastric cancer cells, qRT-PCR was used to detect the expression of HEIH in gastric cancer and nontumor gastric tissues. HEIH interference sequence was constructed to downregulate HEIH expression in MGC-803 and BGC-823 cell lines. CCK8, clonogenesis, and Transwell assay were used to detect the effects of HEIH on proliferation and invasion of tumor cells. The protein levels of STAT3, p-STAT3, P62, and LC3 were detected by Western blotting. The results showed that HEIH was highly expressed in gastric cancer (P < 0.01). Interference of HEIH expression in MGC-803 and BGC-823 cells reduced the proliferation and invasion of gastric cancer cells, and the results were statistically significant (P < 0.05). HEIH acts as a miRNA sponge for miR-4500. HEIH promotes gastric cancer development by inhibiting miR-4500. STAT3 is a downstream target of miR-4500. HEIH inhibits autophagy and promotes glycolysis. In conclusion, HEIH is highly expressed in gastric cancers. HEIH promotes malignant proliferation and development of gastric cancer cells. HEIH may be a new candidate site for pathological diagnosis and molecular drug therapy for future clinical treatment of gastric cancer.

High Expression of lncRNA HEIH is Helpful in the Diagnosis of Non-Small Cell Lung Cancer and Predicts Poor Prognosis.

BackgroundThis study aims to investigate the expression and clinical value of long non-coding RNA (lncRNA) HEIH in peripheral blood of patients with non-small cell lung cancer (NSCLC).MethodsHealthy subjects (N=70), patients with lung squamous cell carcinoma (LUSC, N=70) and patients with lung adenocarcinoma (LUAD, N=80) were included. LncRNA HEIH expression in peripheral blood of included subjects was detected using RT-qPCR. According to the median expression of lncRNA HEIH, LUSC and LUAD patients were allocated into lncRNA HEIH high/low expression groups. The correlation between lncRNA HEIH and clinical indicators of patients was analyzed; Logistic multifactor regression was used to analyze the independent risk factors influencing lncRNA HEIH level. Receiver-operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of lncRNA HEIH and carcinoembryonic antigen (CEA) in LUSC/LUAD patients. MedCalc-Comparison of ROC curves was used to compare the area under ROC curve. The cumulative survival rates of lncRNA HEIH high/low expression group were analyzed by Kaplan–Meier curve. COX multivariate analysis was used to assess the independent factors affecting prognosis of NSCLC.ResultsLncRNA HEIH in peripheral blood of LUSC/LUAD patients was higher than that in healthy controls, with no evident difference between LUSC and LUAD groups. In LUSC/LUAD patients, TNM stage, lymph node metastasis, distal metastasis, and CEA were independent risk factors affecting lncRNA HEIH; patients with high lncRNA HEIH expression had larger pack-years and tumor size, higher CEA level and tumor stage, and higher risk of lymph node metastasis and distal metastasis. LncRNA HEIH had higher diagnostic efficiency than CEA in NSCLC patients. High expression of lncRNA HEIH predicted poor prognosis in patients with NSCLC and was an independent risk factor for prognosis of NSCLC.ConclusionHigh expression of lncRNA HEIH is helpful in the diagnosis of NSCLC and predicts poor prognosis.

Sinomenine Inhibits the Progression of Bladder Cancer Cells by Downregulating LncRNA-HEIH Expression.

Background Sinomenine has been reported to effectively repress the progression of lung cancer and breast cancer. However, the effects of sinomenine in bladder cancer are not well understood. The purpose of this study was to evaluate the effects of sinomenine in bladder cancer. Methods The mRNA expression of HEIH in bladder cancer cells was measured by RT-qPCR. T24 and SW780 cells were treated with sinomenine for 24 hours. Cell viability was detected by the MTT assay. Cell migration and invasion were detected by the transwell assay. Western blotting assay was performed to assess the protein expression of Bcl-2, Bax, and caspase-3. Results Sinomenine significantly suppressed cell viability in T24 and SW780 cells. Moreover, cell migration and invasion were significantly inhibited by sinomenine. Sinomenine accelerated the expression of Bax and caspase-3 but decreased the expression of Bcl-2. HEIH was upregulated in bladder cancer cells compared with normal bladder epithelial cells. Besides this, we noticed that HEIH knockdown blocked cell proliferation, migration, and invasion but facilitated cell apoptosis in bladder cancer cells. Additionally, HEIH reversed the suppression of the progression induced by sinomenine. Conclusion Sinomenine was observed to suppress cell progression of bladder cancer cells by inhibiting HEIH expression. Our findings suggested that the use of sinomenine might be an effective treatment for bladder cancer.

LncRNA HEIH accelerates cell proliferation and inhibits cell senescence by targeting miR-3619-5p/CTTNBP2 axis in ovarian cancer.

Epithelial ovarian cancer is the most lethal malignancy in gynecology. Numerous studies have confirmed that long noncoding RNAs (lncRNAs) are abnormally expressed in ovarian cancer and are closely associated with the cell proliferation and senescence in cancers. However, the role and underlying molecular mechanism of long noncoding RNA high expression in hepatocellular carcinoma (HEIH) in ovarian cancer remain unknown. Experiments including Real-time quantitative polymerase chain reaction, RNA immunoprecipitation, luciferase reporter, Fluorescence in situ hybridization, western blot, colony formation assays, β-galactosidase senescence assay, cell apoptosis, proliferation, invasion, and migration assays were applied to investigate the role of HEIH in ovarian cancer. The data were expressed as the mean ± standard deviation. Student t test was used to compare the data between two groups. The one-way analysis of variance was applied to compare the data among multiple groups with Tukey post hoc test. All experiments were repeated three times. P < 0.05 was considered statistically significant. Herein, HEIH expression was found to be up-regulated in ovarian cancer tissues (n = 25; twofold higher than normal tissues, P < 0.05) and cell lines (sixfold higher than normal ovarian epithelial cell line on average, P < 0.05), and high HEIH expression predicted poor prognosis (survival rate is about 25% after 40 mo; P < 0.05). Moreover, we found that HEIH accelerated proliferation, migration, and invasion, whereas inhibited cell senescence in ovarian cancer (P < 0.05). In mechanism, HEIH was confirmed to serve as a sponge for miR-3619-5p, and miR-3619-5p counteracted HEIH-mediated regulation of ovarian cancer (P < 0.05). Besides, cortactin-binding protein 2 (CTTNBP2) was found to be the downstream target of miR-3619-5p. Rescue assays validated that CTTNBP2 up-regulation significantly reversed the inhibitory effects of HEIH knockdown on ovarian cancer progression (P < 0.05). Furthermore, we found that HEIH facilitated tumor growth in vivo by regulating CTTNBP2 expression (P < 0.05). In conclusion, our research revealed that HEIH accelerated cell proliferation, migration and invasion, whereas inhibited cell senescence in ovarian cancer via targeting the miR-3619-5p/CTTNBP2 axis. These findings may be valuable for finding new therapeutic targets to improve ovarian cancer treatment.

LncRNA HEIH, an indicator of high malignancy and poor prognosis, functions as an oncogene in breast cancer.

Long non-coding RNA high expression in hepatocellular carcinoma (lncRNA HEIH) acts as an oncogene in multiple tumors, including hepatocellular carcinoma, colorectal cancer, melanoma and non-small cell lung cancer. However, the role of HEIH in breast cancer remains unknown. The present study focused on the clinical significance and biological function of HEIH in breast cancer. Specifically, the expression levels of HEIH in breast cancer tissues and breast cancer cell lines were investigated. The results indicated high expression levels of HEIH in human breast cancer tissues, and its expression was positively associated with malignancy status and poor disease prognosis. High expression levels of HEIH were detected in the breast cancer cell lines, including MCF-7, SK-BR-3, MDA-MB-231 and MDA-MB-468. These data were consistent with those derived from the in vivo study. Therefore, small interfering RNA was used to knockdown HEIH expression in order to explore whether HEIH exhibits an oncogenic function in breast cancer. Following HEIH knockdown, the proliferative and metastatic activity of MDA-MB-231 cells was decreased, whereas the induction of cell apoptosis was increased. These results suggested the oncogenic role of HEIH in breast cancer and the potential application of HEIH as an index of malignancy and poor prognosis in breast cancer.

LncRNA-HEIH suppresses hepatocellular carcinoma cell growth and metastasis by up-regulating miR-199a-3p.

The aim of this study was to explore the functional changes of long non-coding ribonucleic acid (lncRNA)-HEIH on hepatocellular carcinoma (HCC) Huh7 and Hep3B cells. The expression changes of HEIH in 18 pairs of HCC tissues and adjacent normal tissues were detected by quantitative real time-polymerase chain reaction (qRT-PCR). According to its expression changes in HCC cells silenced by short hairpin ribonucleic acid (shRNA) transfection in vitro, these cells were divided into sh-HEIH group and sh-NC group. The effects of lowly expressed HEIH on the proliferation, migration and apoptosis of HCC cells were examined through functional assays. Western blotting was adopted to determine the expression changes of epithelial-mesenchymal transition (EMT) proteins, vimentin, matrix metalloproteinase (MMP)-2 and MMP-3. In addition, the role of HEIH downstream effector micro RNA (miR)-199a-3p in HCC was explored. Compared with adjacent normal tissues, HEIH was highly expressed in HCC tissues (p<0.01). HEIH silencing significantly inhibited the proliferation and migration, but induced the apoptosis of Huh7 cells (p<0.05). The expressions of vimentin and MMP-2 in sh-HEIH group were remarkably lower than those in sh-NC group (p<0.05). Furthermore, miR-199a-3p was identified as the downstream effector of HEIH. The expression of miR-199a-3p increased markedly in Huh7 and Hep3B cells with silenced HEIH expression (p<0.01). Moreover, when miR-199a-3p expression was inhibited, the effects of HEIH on Huh7 and Hep3B cells were weakened, manifested as notably enhanced cell proliferation and migration capabilities (p<0.05). LncRNA-HEIH suppresses HCC cell growth and metastasis by up-regulating miR-199a-3p. Our findings suggest that HEIH may be a promising target for HCC treatment.

LncRNA HEIH promotes cell proliferation, migration and invasion in cholangiocarcinoma by modulating miR-98-5p/HECTD4

To date, a large set of long non-coding RNAs (lncRNAs) have been identified in tumorigenesis and progression. The present study focused on functions and mechanisms of HEIH in cholangiocarcinoma (CHOL). We started this study by testing the expression of HEIH in CHOL tissues by qRT-PCR technology. Next, loss-of-function experiments demonstrated the oncogenic nature of HEIH in CHOL. We also used bioinformatics tools to select miRNAs and mRNAs for support of the ceRNA network. Mechanistic experiments including RIP assay, luciferase reporter assay were carried out for further confirmation of binding situation among ceRNA molecules. At last, rescue experiments proved the ceRNA axis in CHOL. According to the results, HEIH expression was up-regulated in CHOL tissues and cells. Functionally, knockdown of HEIH attenuated cell proliferation, migration and invasion. Mechanistically, bioinformatics analysis, RIP assay and luciferase assay verified the ceRNA network among HEIH, miR-98-5p and HECTD4. Rescue experiments further demonstrated the oncogenic role of HEIH and HECTD4. The final in vivo experiments suggested that knockdown of HEIH restrained tumor growth both in weight and volume. In conclusion, HEIH promoted CHOL tumorigenesis and progression by miR-98-5p/HECTD4 axis, which opens up a new insight for CHOL therapeutics.

LncRNA HEIH Enhances Paclitaxel-Tolerance of Endometrial Cancer Cells via Activation of MAPK Signaling Pathway.

This study aimed to investigate the function of lncRNA HEIH on promoting endometrial cancer cells' tolerance of paclitaxel (PTX). LncRNA HEIH expression was measured by QRT-PCR in endometrial cancer tissues, human healthy tissues and cell lines. The PTX-resistant endometrial cancer cells (Ishikawa-RE and HHUA-RE) were intermittently exposed to increase concentrations of PTX and were constructed as evidenced by MTT assay. Besides, the specific siRNA of HEIH (siHEIH) and pcDNA3.1-HEIH plasmid transfection were utilized to alter the expression of HEIH in the cells and investigate the effects of HEIH on resistance to PTX in endometrial cancer cells. Moreover, MTT, colony formation and apoptosis analysis were taken advantage to evaluate cell viability and proliferation when treated with PTX. Then, differential genes in PTX-resistant and HEIH-knock-down PTX-resistant endometrial cancer cells were screened out by microarray analysis. Finally, gene-set enrichment analysis was used to predict the promising signaling pathway of HEIH and western blotting analysis were performed to verify the relevant genes expression of MAPK signaling pathway. LncRNA HEIH, the dysregulation of which involved in production of drug-resistance, was overexpressed in PTX-resistant endometrial cancer cells. Up-regulating HEIH would activate MAPK pathway, promote chemo-resistance of endometrial cancer cells and enhance cell proliferation and viability, whereas silencing HEIH depressed the MAPK signaling pathway, contributed to restoring chemo-sensitivity to PTX and repressed cell physiological process. Down-regulating lncRNA HEIH expression reversed the PTX-resistance of endometrial cancer cells through MAPK signaling pathway.

LncRNA HEIH regulates cell proliferation and apoptosis through miR-4458/SOCS1 axis in triple-negative breast cancer.

Hepatocellular carcinoma up-regulated EZH2-associated long non-coding RNA (HEIH) is a newly discovered lncRNA and has been suggested to be dysregulated in human cancers. However, the role of HEIH in triple-negative breast cancer (TNBC) was still unknown. Thus, the aim of our study was to investigate the clinical significance and biological function of HEIH in TNBC. In our study, we found that HEIH was overexpressed in TNBC tissues and cell lines compared with adjacent normal mammary tissues and normal mammary epithelial cell line, respectively. In addition, we conducted bioinformatic analysis, and found that HEIH harbors a potential miR-4458-binding site. Furthermore, we observed that HEIH and miR-4458 had a high correlation score in TNBC tissues, and HEIH directly binds to miR-4458, and negatively regulates miR-4458 expression in TNBC cells. The in vitro cell proliferation and apoptosis assays suggested down-regulation of HEIH inhibited TNBC cell proliferation and promoted apoptosis through regulating miR-4458/SOCS1 axis. Finally, we found that TNBC patients with tumor size ≥ 5cm or advanced clinical stage had higher levels of HEIH expression than patients with tumor size <5cm or early clinical stage. In conclusion, HEIH functions as an oncogenic lncRNA that is overexpressed in TNBC and associated with clinical progression, and regulates TNBC cell proliferation and apoptosis through miR-4458/SOCS1 axis.

Retracted: Silence of lncRNA HEIH suppressed liver cancer cell growth and metastasis through miR‐199a‐3p/mTOR axis

High expression in hepatocellular carcinoma (HEIH) is an long noncoding RNA (lncRNA) which is highly expressed in hepatocellular carcinoma (HCC). Aberrant expression of HEIH is implicated in regulating HCC cells growth and metastasis. This study attempted to illustrate the effects of HEIH on HCC cell lines. The expression changes of HEIH in HCC tumor tissues and the paracancerous tissues derived from 20 patients with HCC were tested. Effects of HEIH on Huh7 and Hep3B cells viability, apoptosis, migration, and invasion were assessed by silencing HEIH in vitro. Furthermore, downstream effector and signaling of HEIH were studied. As compared with the paracancerous tissues, the HEIH expression was highly expressed in tumor tissues. Silence of HEIH significantly reduced Huh7 and Hep3B cells viability, migration, and invasion, but induced apoptosis. It was coupled with the downregulated CyclinD1, Bcl-2, MMP-2, MMP-8, Vimentin, the upregulated p53, Bax, as well as the cleaved caspase-3. MicroRNA (miR)-199a-3p was identified as a downstream effector of HEIH, as its expression was upregulated by HEIH silence, and the functional effects of HEIH on Huh7 and Hep3B cells were all attenuated when miR-199a-3p expression was suppressed. Furthermore, HEIH silence suppressed the activation of mTOR signaling via upregulating miR-199a-3p. HEIH silence might be a promising target for suppressing HCC cells growth and metastasis. Silence of HEIH exerted its antitumor properties possibly through upregulating miR-199a-3p, and thereby blockage of mTOR signaling.

Microarray profiling and co-expression network analysis of lncRNAs and mRNAs in ovarian cancer

Dysregulated long noncoding RNAs (lncRNAs) are involved in the pathogenesis and development of human diseases, such as epithelial ovarian cancer (EOC). In this study, we identified EOC-related lncRNAs and performed lncRNA and mRNA microarray analyses using IOSE80, a normal ovary cell line, and two ovarian carcinoma cell lines (SKOV3 and SKOV3/DDP) to investigate the potential roles of lncRNAs in EOC. lncRNA-HEIH expression in EOC tissues and cell lines was measured by quantitative real-time polymerase chain reaction (qPCR). In addition, we generated a lncRNA–mRNA co-expression network in order to identify lncRNA-expression trends and potential lncRNA target genes. Cell viability, migration, and invasion were determined by Cell Counting Kit-8, transwell assay, and wound-healing assay, respectively, and apoptosis was analyzed by flow cytometry. We identified 3527 differentially expressed lncRNAs upon comparison of the lncRNA profiles from IOSE80 with those of SKOV3 cell lines, with 11 differentially expressed lncRNAs confirmed by qPCR. Both pathway and gene ontology analyses demonstrated the involvement of lncRNAs, especially HEIH and LINC-PINT, in multiple biological processes. Furthermore, in vitro knockdown experiments confirmed that suppression of HEIH expression inhibited EOC cell proliferation. Our findings provide a foundation for further research into the role of these lncRNAs in EOC carcinogenesis and progression.

Long noncoding RNA HEIH promotes the proliferation and metastasis of non–small cell lung cancer

This study is aimed to explore the functions of long noncoding RNA (lncRNA) HEIH on the proliferation as well as metastasis of non-small cell lung cancer (NSCLC). HEIH was shown to be increased in NSCLC by a microarray study on lncRNA profiling. We detected the expression of HEIH in different human NSCLC lines and tissues by quantitative real-time PCR. After gain- and loss-of-function approaches in A549 and Calu-1 cells, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, thiazolyl blue tetrazolium bromide (MTT) assays and a colony formation assay were applied to test the proliferative activity of cells, and the apoptosis of cells was measured by flow cytometry. Western blot analysis was used to evaluate the protein expression, and the effects of lncRNA HEIH on cell migratory and invasive abilities of A549 and Calu-1 cells were evaluated using wound healing and transwell assays. In our study, we confirmed the elevated expression of HEIH in NSCLC tissues and cell lines compared with the normal ones. After constructing A549 and Calu-1 cells with altered HEIH expression by transient transfection, cell viability was found to be positively regulated by the HEIH level. Moreover, overexpression of HEIH accelerated the cell migrating rate and increased the invasive cell number according to the results of a wound healing assay and transwell assay. HEIH could accelerate the proliferation and metastasis of NSCLC, providing a novel therapeutic target for clinical treatment.

LncRNA-HEIH in serum and exosomes as a potential biomarker in the HCV-related hepatocellular carcinoma.

Chronic hepatitis C (CHC) is a contagious liver disease that results from infection with the hepatitis C virus (HCV). The most serious consequence of CHC is HCV-related hepatocellular carcinoma (HCC). To illustrate the clinical significance of lncRNA HEIH expression in serum and exosomes in the development of HCV-related HCC. Thirty-five CHC, twenty-two HCV-induced cirrhosis and ten HCV-related HCC patients in Huzhou Central Hospital from January 2016 to September 2016 were recruited in the present study. Basic patient information, clinical serological indicators, and clinical imaging data were investigated and analyzed. Serum samples were collected from patients after receiving informed consent. Exosomes were extracted from the serum, and electron microscopy was used to observe the ultrastructure of exosomes. Quantitative PCR was used to detect lncRNA HEIH gene expression in serum and exosomes. The changes in the ALT, GGT, HDL, INR, Alb and AFP levels in the patients with HCV-induced cirrhosis and HCV-related HCC were statistically significant. In patients with HCV-related HCC, lncRNA-HEIH expression in serum and exosomes was increased, but the ratio of lncRNA-HEIH expression in serum versus exosomes was decreased compared to patients with CHC.