PM2.5 regulates the progression of lung adenocarcinoma through the axis of HCG18, miR-195 and ATG14.

Relevant studies have indicated the association of HCG18 with tumour occurrence and progression. In this study, we observed that PM2.5 can enhance the growth of lung adenocarcinoma cells by modulating the expression of HCG18. Further investigations, including overexpression and knockout experiments, elucidated that HCG18 suppresses miR-195, which in turn upregulates the expression of ATG14, resulting in the upregulation of autophagy. Consequently, exposure to PM2.5 leads to elevated HCG18 expression in lung tissues, which in turn increases Atg14 expression and activates autophagy pathways through inhibition of miR-195, thereby contributing to oncogenesis.

Blocking lncRNA HCG18 re-sensitizes Taxol resistant lung cancer cells to Taxol through modulating the miR-34a-5p/HDAC1 axis.

Lung cancer is one of the most frequently diagnosed cancers worldwide, associated with a poor survival rate. Taxol (Paclitaxel) is commonly used as a chemotherapeutic treatment for advanced lung cancers. While Taxol has improved clinical outcomes for lung cancer patients, a significant number of them develop resistance to Taxol, resulting in treatment failure. The role of the long noncoding RNA HCG18 in lung cancer and Taxol resistance has not yet been fully understood. To investigate this, we examined the expression of HCG18 and miR-34a-5p in lung tumors and normal lung tissues using qRT-PCR. We also assessed Taxol resistance through cell viability and apoptosis assays. Through the starBase online service, we analyzed the interactions between lncRNA and mRNA as well as miRNA and mRNA. We further validated the association between lncRNA and miRNA through luciferase and RNA pull-down assays. Our findings demonstrated that HCG18 was significantly upregulated in lung cancer tissues compared to normal lung tissues. Silencing HCG18 increased the sensitivity of lung cancer cells to Taxol. Additionally, our study established a Taxol-resistant cell line and observed a substantial upregulation of HCG18 in Taxol-resistant lung cancer cells. Bioinformatic analysis predicted that HCG18 could bind to miR-34a-5p, forming a competing endogenous RNA network, which was confirmed through luciferase assay. We found that miR-34a-5p was downregulated in lung cancer tissues and negatively correlated with Taxol resistance, as it directly bound to the 3'UTR region of HDAC1. Further results showed that inhibition of HCG18 significantly increased miR-34a-5p expression and sensitized lung cancer cells to Taxol. This sensitization could be reversed by inhibiting miR-34a-5p. Finally, we demonstrated in a xenograft mouse model that inhibition of HCG18 sensitized Taxol-resistant lung cancer cells to Taxol treatment by modulating the miR-34a-5p-HDAC1 axis. In conclusion, our in vitro and in vivo results uncover a novel molecular mechanism by which HCG18 promotes Taxol resistance through modulation of the miR-34a-5p/HDAC1 axis. These findings contribute to the diagnosis and treatment of chemo-resistant lung cancer.

Identification and analysis of MSC-Exo-derived LncRNAs related to the regulation of EMT in hypospadias.

OBJECTIVE: This study aims to screen the differentially expressed long non-coding RNAs (DELncRNAs) related to the regulation of epithelial-mesenchymal transition (EMT) in hypospadias in mesenchymal stem cell-derived exosomes (MSC-Exons) and explore the potential mechanism of these lncRNAs for the EMT in hypospadias. METHODS: In this study, the microarray data related to MSC-Exos and hypospadias were downloaded from Gene Expression Omnibus (GEO). Besides, the lncRNAs highly expressed in MSC-Exos and the differentially expressed mRNAs and lncRNAs in children with hypospadias were screened, respectively. In addition, the lncRNAs enriched in MSC-Exos and differentially expressed lncRNAs in hypospadias were intersected to obtain the final DElncRNAs. Moreover, the co-expression interaction pairs of differentially expressed lncRNAs and mRNAs were analyzed to construct a Competing Endogenous RNA (ceRNA) network. Finally, the candidate lncRNAs in exosomes were subjected to in vitro cell function verification. RESULTS: In this study, a total of 4 lncRNAs were obtained from the microarray data analysis. Further, a ceRNA regulatory network of MSC-Exo-derived lncRNAs related to the regulation of EMT in hypospadias was constructed, including 4 lncRNAs, 2 mRNAs, and 6 miRNAs. The cell function verification results indicated that the exosomes secreted by MSCs may transport HLA complex group 18 (HCG18) into target cells, which promoted the proliferation, migration, and EMT of these cells. CONCLUSION: MSC-Exo-derived lncRNA HCG18 can enter target cells, and it may be involved in the regulation of EMT in hypospadias through the ceRNA network.

The role of lncRNA HCG18 in human diseases.

A substantial number of long noncoding RNAs (lncRNAs) have been identified as potent regulators of human disease. Human leukocyte antigen complex group 18 (HCG18) is a new type of lncRNA that has recently been proven to play an important role in the occurrence and development of various diseases. Studies have found that abnormal expression of HCG18 is closely related to the clinicopathological characteristics of many diseases. More importantly, HCG18 was also found to promote disease progression by affecting a series of cell biological processes. This article mainly discusses the expression characteristics, clinical characteristics, biological effects and related regulatory mechanisms of HCG18 in different human diseases, providing a scientific theoretical basis for its early clinical application.

LncRNA HCG18 affects diabetic cardiomyopathy and its association with miR-9-5p/IGF2R axis.

This paper aimed to investigate the role of lncRNA HCG18 (HCG18) in the progression of diabetic cardiomyopathy (DCM) and potential mechanisms. Streptozocin (STZ) was used to induce DCM model in rats, which was confirmed by blood glucose concentration, body weight, and HE staining. Myocardial apoptosis was detected by TUNEL. H9c2 cardiomyocytes were used to construct cell models of DCM through treatment of high glucose. The results showed that HCG18 was overexpressed in STZ induced DCM rat model and high glucose induced H9c2 cardiomyocytes. Si-HCG18 significantly increased cell viability, reduced cell apoptosis, attenuated activities of myocardial enzymes and enhanced activities of antioxidant enzymes in STZ induced DM model and high glucose induced H9c2 cardiomyocytes, while the results of upregulation of HCG18, in high glucose induced H9c2 cardiomyocytes, were opposite with that of si-HCG18. MiR-9-5p was a target of HCG18, and which was down-regulated in cardiomyocytes of DCM. The overexpression of miR-9-5p could neutralize the high glucose induced cardiomyocyte injury, and the silence of miR-9-5p could reverse the effect of si-HCG18 on high glucose induced cardiomyocytes. MiR-9-5p could directly target to IGF2R, and IGF2R was overexpressed in cardiomyocytes of DCM. Up-regulation of IGF2R can reverse the protective effect of si-HCG18 on cardiomyocytes. Taken together, HCG18 is significantly increased in cardiomyocytes of DCM. Down-regulation of HCG18 can improve cardiomyocyte injury through miR-9-5p/IGF2R axis in DCM.

LncRNA HCG18 promotes inflammation and apoptosis in intervertebral disc degeneration via the miR-495-3p/FSTL1 axis.

Intervertebral disc degeneration (IDD) causes pain in the back and neck. This study investigated the role of long non-coding RNA HLA complex group 18 (HCG18) in a cell model of IDD. An IDD model was established by stimulating nucleus pulposus (NP) cells with interleukin (IL)-1ß. MTT assay was performed to evaluate NP cell viability. The apoptosis was detected by flow cytometry. The expressions of HCG18, microRNA (miR)-495-3p, and follistatin-like protein-1 (FSTL1) were measured by RT-qPCR. The interactions of miR-495-3p with HCG18 and FSTL1 were analyzed by luciferase reporter assay. IL-1ß stimulation upregulated HCG18 and FSTL1, but downregulated miR-495-3p in NP cells. Silencing of HCG18 or FSTL1, as well as miR-495-3p overexpression in NP cells alleviated IL-1ß-induced apoptosis and inflammation of NP cells. Both HCG18 and FSTL1 had binding sites for miR-495-3p. Overexpression of FSTL1 abolished the effects of HCG18 silencing on IL-1ß-induced apoptosis and inflammation. The HCG18/miR-495-3p/FSTL1 axis is essential for IDD development. Therapeutic strategies targeting this axis may be used for IDD treatment.

Expression and diagnostic value of lncRNA HCG18 in gestational diabetes mellitus.

OBJECTIVES: Gestational diabetes mellitus (GDM) is the first type of diabetes induced by abnormal maternal glucose metabolism after pregnancy. Long non-coding RNA (lncRNA) has been found to be of great value in the study of its pathogenesis and treatment. This study aimed to explore the expression and diagnostic value of lncRNA HCG18 in GDM. MATERIAL AND METHODS: The expression levels of HCG18 in serum of participating GDM patients and healthy controls were detected by polymerase chain reaction (RT-qPCR). The correlation between the expression of HCG18 and the blood glucose level was clarified by the detection of blood glucose levels in GDM patients. The receiver operating characteristic curve (ROC) was used to evaluate the clinical diagnostic value of HCG18 for GDM. Furthermore, multivariate logistic analysis was used to verify the diagnostic value of HCG18 in GDM. RESULTS: This study concluded that the expression level of HCG18 was upregulated in the serum of GDM patients compared with the control group. ROC curve showed that the AUC was 0.916, the sensitivity was 80.5%, the specificity was 90.2%, and multivariate logistic regression analysis verified that HCG18 (OR = 6.984, 95% CI = 3.751-13.005, p < 0.001) was significantly associated with GDM, which suggesting that HCG18 has diagnostic significance for GDM. In addition, the expression of HCG18 was positively correlated with fasting blood glucose, 1h blood glucose and 2 h blood glucose of patients. CONCLUSIONS: LncRNA HCG18 was elevated in patient serum and might serve as a diagnostic biomarker for GDM.

LncRNA HCG18 loaded by polymorphonuclear neutrophil-secreted exosomes aggravates sepsis acute lung injury by regulating macrophage polarization.

Polymorphonuclear neutrophils (PMNs) exert significant roles in septic acute lung injury (ALI). Accumulating evidence suggests that PMN-derived exosomes (PMN-exo) are a novel subcellular entity that is the fundamental link between PMN-driven inflammation and tissue damage. However, the role of PMN-exo in septic ALI and the underlying mechanisms remain unclear. Tumor necrosis factor-α (TNF-α), a key regulator of innate immunity in septic ALI, was used to induce PMN activation in vitro. Using an in vitro co-culture system, the rat alveolar macrophage cell line NR8383 was co-cultured with TNF-α-stimulated PMN-released exosomes (TNF-α-exo) to further confirm the results of the in vitro studies and explore the underlying mechanisms involved. A septic lung injury model was established by cecal ligation and puncture surgery, and PMN-exo were injected into septic mice through the tail vein, and then lung injury, inflammatory release, macrophage polarization, and apoptosis were examined. The results reported that TNF-α-exo promoted the activation of M1 macrophages after i.p. injection in vivo or co-culture in vitro. Furthermore, TNF-α-exo affected alveolar macrophage polarization by delivering HCG18. Mechanistic studies indicated that HCG18 mediated the function of TNF-α-exo by targeting IL-32 in macrophages. In addition, tail vein injection of si-HCG18 in septic mice significantly reduced TNF-α-exo-induced M1 macrophage activation and lung macrophage death, as well as histological lesions. In conclusion, TNF-α-exo-loaded HCG18 contributes to septic ALI by regulating macrophage polarization. These findings may provide new insights into novel mechanisms of PMN-macrophage polarization interactions in septic ALI and may provide new therapeutic strategies for patients with sepsis.

The regulatory role of LncRNA HCG18 in various cancers.

As a member of long non-coding RNAs (lncRNAs), LncRNA HLA complex group 18 (HCG18) has recently become the focus of cancer research. As outlined in this review, LncRNA HCG18 has been reported to be dysregulated in various cancers development and appears to be activated in a variety of tumors, including clear cell renal cell carcinoma (ccRCC), colorectal cancer (CRC), gastric cancer (GC), hepatocellular carcinoma (HCC), laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC), lung adenocarcinoma (LUAD), nasopharyngeal cancer (NPC), osteosarcoma (OS), and prostate cancer (PCa). Furthermore, the expression of lncRNA HCG18 decreased in bladder cancer (BC) and papillary thyroid cancer (PTC). Overall, the presence of these differential expressions suggests the clinical value of HCG18 in cancer therapy. Additionally, lncRNA HCG18 influences various biological processes of cancer cells. This review summarizes the molecular mechanisms of HCG18 in cancer development, highlights reported the abnormal expression of HCG18 found in various cancer types, and aims to discuss the potential of HCG18 as a target for cancer therapy.

The role of long non-coding RNA HCG18 in cancer

The incidence of cancer is increasing worldwide and is becoming the most common cause of death. Identifying new biomarkers for cancer diagnosis and prognosis is important for developing cancer treatment strategies and reducing mortality. Long non-coding RNAs (lncRNAs) are non-coding, single-stranded RNAs that play an important role as oncogenes or tumor suppressors in the occurrence and development of human tumors. Abnormal expression of human leukocyte antigen complex group 18 (HCG18) is observed in many types of cancer, and its imbalance is closely related to cancer progression. HCG18 regulates cell proliferation, invasion, metastasis, and anti-apoptosis through a variety of mechanisms. Therefore, HCG18 is a potential tumor biomarker and therapeutic target. However, the therapeutic significance of HCG18 has not been well studied, and future research may develop new intervention strategies to combat cancer. In this study, we reviewed the biological function, mechanism, and potential clinical significance of HCG18 in various cancers to provide a reference for future research (AU)

Silencing lncRNA HCG18 regulates GPX4-inhibited ferroptosis by adsorbing miR-450b-5p to avert sorafenib resistance in hepatocellular carcinoma.

Ferroptosis is potential to relieve drug resistance in hepatocellular carcinoma (HCC). Glutathione peroxidase 4 (GPX4) is a critical modulator of ferroptosis. This study discussed the mechanism of GPX4-inhibited ferroptosis in sorafenib resistance in HCC. HCG18 in HCC cells was detected. Sorafenib resistant (SR) cell line Huh7-SR cells were treated with sorafenib (0, 2.5, 5, 7.5, 10 µM). After silencing HCG18 in Huh7-SR cells, cell activity, proliferation and apoptosis were detected. The levels of iron, the concentration of MDA, GSH and lipid reactive oxygen species (ROS) were measured to evaluate the ferroptosis. The downstream mechanism of HCG18 was predicted and verified. Huh7-SR cells were infected with lentivirus sh-HCG18 to establish xenograft tumor model. HCG18 was elevated in HCC cells and associated with sorafenib resistance. Silencing HCG18 inhibited cell proliferation, promoted apoptosis, and impaired sorafenib resistance. Ferroptosis was inhibited in Huh7-SR cells, while silencing HCG18 inhibited sorafenib resistance by promoting ferroptosis. GPX4 overexpression averted the promotion of sh-HCG18 on ferroptosis, thereby reducing sorafenib resistance. HCG18 sponged miR-450b-5p to regulate GPX4. Collectively, Silencing HCG18 inhibits GPX4 by binding to miR-450b-5p, promotes GPX4-inhibited ferroptosis, and averts sorafenib resistance in HCC.

LncRNA HCG18 Promotes Osteosarcoma Cells Proliferation, Migration, and Invasion in by Regulating miR-34a/RUNX2 Pathway.

Osteosarcoma (OS) is a type of tumor with high malignant behaviors. Increasing investigates have confirmed that long non-coding RNA HLA complex group 18 (lncRNA HCG18) acted as a tumor-promoting factor in multiple tumors. Nevertheless, the underlying mechanism of HCG18 on OS remains largely unclear. HCG18, miR-34a, and runt-related transcription factor 2 (RUNX2) expressions were detected by quantitative real-time PCR (RT-qPCR) or western blotting assays, respectively. The underlying tumorigenic phenotypes were detected by MTT, wound healing, transwell invasion, western blotting assays. Molecular interactions were verified by dual-luciferase report assay. HCG18 and RUNX2 were notably enhanced, whereas miR-34a was decreased in OS tumor tissues and cell lines. Functional experiments uncovered that HCG18 silencing significantly inhibited the capabilities of proliferation, migration, and invasion, while overexpression of HCG18 play the opposite roles. Furthermore, HCG18 directly bound to miR-34a, and miR-34a was confirm to be a negative regulator of RUNX2. Interestingly, the anti-tumor effects of HCG18 silencing were attenuated by miR-34a inhibitor and RUNX2 overexpression. Taken together, the present study suggested that HCG18 promoted the malignant biological behaviors of OS through regulating the miR-34a/RUNX2 pathway, implying HCG18 might serve as a new target for OS treatment.

Long noncoding RNA HCG18 Promotes Extracellular Matrix Degradation of Nucleus Pulposus Cells in Intervertebral Disc Degeneration by Regulating the miR-4306/EPAS1 Axis.

BACKGROUND: Intervertebral disc degeneration is a very common disease worldwide and the leading cause of low back pain. Long noncoding RNAs are novel players in intervertebral disc degeneration and have multiple functions. This study explored the role of long noncoding RNA HCG18 in regulating extracellular matrix (ECM) degradation in nucleus pulposus cells (NPCs) during intervertebral disc degeneration. METHODS: NPCs were subjected to interleukin-1ß to induce a degenerative model of NPCs. Cell viability was assessed using Cell Counting Kit-8 assay. Messenger RNA and protein expressions were examined by real-time quantitative polymerase chain reaction and Western blot. The location of HCG18 was determined by nucleocytoplasmic separation assay. The binding relationships between HCG18, MIR4306, and EPAS1 were verified by dual luciferase reporter gene assay and/or RNA immunoprecipitation assay. RESULTS: HCG18 was highly expressed in interleukin-1ß-induced degenerated NPCs, which was associated with reduced collagen II and aggrecan expression and increased MMP-13 and ADAMTS-4 expression. HCG18 knockdown could remarkably inhibit ECM degradation in IL-1ß-induced degenerated NPCs, while HCG18 overexpression had the opposite effect. Our molecular study further revealed that HCG18 could sponge MIR4306, and HCG18 knockdown could suppress ECM degradation in degenerated NPCs by elevating MIR4306 expression. In addition, EPAS1 was identified as the direct target of MIR4306. As expected, MIR4306 overexpression inhibited ECM degradation in degenerated NPCs by downregulating EPAS1. CONCLUSIONS: HCG18 promoted ECM degradation in degenerated NPCs via regulation of the MIR4306/EPAS1 axis.

The role of long non-coding RNA HCG18 in cancer.

The incidence of cancer is increasing worldwide and is becoming the most common cause of death. Identifying new biomarkers for cancer diagnosis and prognosis is important for developing cancer treatment strategies and reducing mortality. Long non-coding RNAs (lncRNAs) are non-coding, single-stranded RNAs that play an important role as oncogenes or tumor suppressors in the occurrence and development of human tumors. Abnormal expression of human leukocyte antigen complex group 18 (HCG18) is observed in many types of cancer, and its imbalance is closely related to cancer progression. HCG18 regulates cell proliferation, invasion, metastasis, and anti-apoptosis through a variety of mechanisms. Therefore, HCG18 is a potential tumor biomarker and therapeutic target. However, the therapeutic significance of HCG18 has not been well studied, and future research may develop new intervention strategies to combat cancer. In this study, we reviewed the biological function, mechanism, and potential clinical significance of HCG18 in various cancers to provide a reference for future research.

LncRNA HCG18 promotes M2 macrophage polarization to accelerate cetuximab resistance in colorectal cancer through regulating miR-365a-3p/FOXO1/CSF-1 axis.

BACKGROUND: Cetuximab (CET) resistance in colorectal cancer (CRC) is responsible to poor prognosis to some extent. M2 macrophage polarization is closely correlated with drug resistance to cancers. Therefore, this study aims to investigate whether the mechanism of HCG18 on CET resistance to CRC involving in M2 macrophage polarization. METHODS: Clinic samples and SW620 cells with/without M0 macrophage co-culture served as experimental subjects. CET treatment was performed to induce SW620 cell resistant to CET. qRT-PCR and western blot were employed to evaluate the mRNA and protein expression of genes. The capabilities of cell viability, proliferation, migration and invasion were examined using CCK-8, clone formation assay and transwell. ELISA was employed to examine the protein concentrations of IL-10 and TGF-ß1. StarBase and luciferase activity assay were conducted to consolidate the interactions among HCG18, miR-365a-3p and FOXO1. RESULTS: In clinical samples and CRC cells, the abundance of HCG18 was enhanced whereas miR-365a-3p was reduced. Besides, HCG18 expression in CET-resistant tumor tissues was higher than that in CET-sensitive tumor tissues and the trend of miR-365a-3p was opposite to that of HCG18. HCG18 knockdown attenuated macrophage-induced CET resistance in SW620 cells and suppressed M2 polarization of THP-1 cells. Mechanistically, HCG18 interacted with miR-365a-3p and miR-365a-3p targeted FOXO1. MiR-365a-3p inhibitor abolished HCG18 knockdown-mediated inhibition of CET resistance, while FOXO1 knockdown compromised the influences of miR-365a-3p inhibitor. FOXO1 could positively regulate CSF-1 expression to promote M2 macrophage polarization and macrophage-induced CET resistance. CONCLUSION: Our results revealed that HCG18 promoted M2 macrophage polarization to facilitate CET resistance to CRC cells through modulating miR-365a-3p/FOXO1/CSF-1 axis.

NUP160 knockdown inhibits the progression of diabetic nephropathy in vitro and in vivo.

Diabetic nephropathy (DN) is a severe diabetic complication and podocyte damage is a hallmark of DN. The Nucleoporin 160 (NUP160) gene was demonstrated to regulate cell proliferation and apoptosis in mouse podocytes. This study explored the possible role and mechanisms of NUP160 in high glucose-triggered podocyte injury. A rat model of DN was established by intraperitoneal injection of 60 mg/kg streptozotocin (STZ). Podocytes were treated with 33 mM high glucose. The effects of the Nup160 on DN and its mechanisms were assessed using MTT, flow cytometry, Western blot, ELISA, RT-qPCR, and luciferase reporter assays. The in vivo effects of NUP160 were analyzed by HE, PAS, and MASSON staining assays. The NUP160 level was significantly upregulated in podocytes treated with 33 mM high glucose. Functionally, NUP160 knockdown alleviated high glucose-induced apoptosis and inflammation in podocytes. Mechanistically, miR-495-3p directly targeted NUP160, and lncRNA HCG18 upregulated NUP160 by sponging miR-495-3p by acting as a ceRNA. Additionally, NUP160 overexpression reversed the effects of HCG18 knockdown in high glucose treated-podocytes. The in vivo assays indicated that NUP160 knockdown alleviated the symptoms of DN rats. NUP160 knockdown plays a key role in preventing the progression of DN, suggesting that targeting NUP160 may be a potential therapeutic strategy for DN treatment.

COMMD2 Upregulation Mediated by an ncRNA Axis Correlates With an Unfavorable Prognosis and Tumor Immune Infiltration in Liver Hepatocellular Carcinoma.

Liver hepatocellular carcinoma (LIHC) seriously endangers the health and quality of life of individuals worldwide. Increasing evidence has underscored that the copper metabolism MURR1 domain (COMMD) family plays important roles in tumorigenesis. However, the specific role, biological function, mechanism and prognostic value of COMMD2 and its correlation with immune cell infiltration in LIHC remain unknown. In this study, we first determined the expression and prognostic potential of COMMD2 in human tumors using The Cancer Genome Atlas (TCGA) data and identified COMMD2 as a potential oncogene in LIHC. High COMMD2 expression was associated with pathological tumor stage and metastasis. Subsequently, noncoding RNAs (ncRNAs) upregulating COMMD2 expression were identified by performing expression, correlation, and survival analyses in combination. The CRNDE/LINC00511/SNHG17/HCG18-miR-29c-3p axis was identified as the most likely ncRNA-associated pathway upstream of COMMD2 in LIHC. Next, the expression profiles of COMMD2 and ncRNAs were validated in LIHC tissues and adjacent normal tissues. Furthermore, COMMD2 was significantly positively correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint molecule expression. Importantly, COMMD2 potentially influenced prognosis by regulating immune cell infiltration in LIHC. Finally, COMMD2 was knocked down in LIHC cell lines using siRNAs for functional assays in vitro, resulting in suppressed cell proliferation and migration. In summary, our findings showed that the ncRNA-mediated upregulation of COMMD2 was associated with an unfavorable prognosis correlated with immune cell infiltration in LIHC.

Long non-coding RNA human leucocyte antigen complex group-18 HCG18 (HCG18) promoted cell proliferation and migration in head and neck squamous cell carcinoma through cyclin D1-WNT pathway.

Emerging evidence has demonstrated that long noncoding RNA (lncRNAs) play a vital role in the development of head and neck squamous cell carcinoma (HNSCC); however, the biological effects and underlying mechanisms of human leukocyte antigen complex group-18 HCG18 (HCG18) have not yet been reported in HNSCC. In this study, we detected the expression of the HCG18 in HNSCC cell lines and patient tissues. We observed that HCG18 was upregulated in HNSCC patient tissues and cell lines. Furthermore, silencing of HCG18 significantly inhibited proliferation, migration, and invasion of HNSCC cells, whereas the opposite effects were detected in the HCG18-overexpressed group. We also found that HCG18 directly binds to the functional protein cyclin D1. Upregulated cyclin D1 reversed the inhibitory effects of HCG18 in HNSCC cell lines and activated the WNT pathway-related proteins (AXIN2, survivin, c-Myc, and ß-catenin) simultaneously. Knockdown of cyclin D1 could accelerate the inhibitory effects of HCG18 and decrease the expression of AXIN2, survivin, c-Myc, and ß-catenin. This indicated that lncRNA HCG18 might be involved in the tumorigenesis of HNSCC via the cyclin D1-WNT pathway. These results suggest that lncRNA HCG18 could act as a promising prognostic biomarker and potential therapeutic target in HNSCC patients.

LncRNA HCG18 facilitates melanoma progression by modulating miR-324-5p/CDK16 axis.

OBJECTIVE: LncRNA HCG18 has been reported to act as a tumor promoter in gastric cancer, hepatocellular carcinoma and nasopharyngeal carcinoma. However, the role of HCG18 in melanoma is still not clear. In this study, we detected the expression and molecular function of HCG18 in melanoma. METHODS: The expression of HCG18 in melanoma cell lines and 50 pairs of melanoma and corresponding non-cancer tissues was detected by RT-qPCR. The relationship between HCG18 and clinicopathology was analyzed. We used HCG18 overexpressing melanoma cell lines A375 and M14, and si-HCG18 to knock down HCG18 expression. CCK-8, clone formation, Transwell assay and FCM were used to explore the effect of HCG18 knockdown on cell proliferation, migration, invasion and apoptosis in melanoma cells. Bioinformatics software was used to predict the downstream miRNA regulated by HCG18, and the downstream target genes regulated by miR-324-5p. Dual-luciferase reporter assay and RNA pull-down assay were used to verify whether miR-324-5p was related to the predicted sequence of HCG18. RESULTS: HCG18 was highly expressed in melanoma tissues and cells. Besides, we found that HCG18 was closely correlated with thickness, TNM stage and metastasis. Functional experiments discovered that HCG18 knockdown restrained cell proliferation, migration and invasion, while promoted cell apoptosis in melanoma cells. HCG18 was confirmed to be a sponge of miR-324-5p, and CDK16 might be a downstream gene of miR-324-5p. HCG18 was found to reverse the effect of miR-324-5p by upregulating CDK16 expression in melanoma cell proliferation, apoptosis, migration and invasion in vitro. CONCLUSION: This study indicated that HCG18 played an essential role in the pathogenesis of melanoma and suggested that HCG18 might be a potential target for the treatment and diagnosis of melanoma.

Long non-coding RNA HCG18 promotes gastric cancer progression by regulating miRNA-146a-5p/tumor necrosis factor receptor-associated factor 6 axis.

Although long non-coding RNAs (lncRNAs) have been demonstrated to be dysregulated in gastric cancer (GC), the function of lncRNA HCG18 (HCG18) in GC is elusive. Therefore, the study was designed to evaluate the underlying mechanism of HCG18 in GC. HCG18 and microRNA 146a-5p (miR-146a-5p) levels in GC were evaluated by RT-qPCR. The effects of miR-146a-5p and HCG18 on GC cell function were examined using Transwell assay, colony formation, and CCK-8 assays. Tumor necrosis factor receptor-associated factor 6 (TRAF6) and p65 expression levels were detected by Western blot. HCG18 and miR-146a-5p target genes were identified using luciferase reporter and bioinformatics assays. HCG18 expression was increased in GC. HCG18 overexpression significantly increased GC cell proliferation, invasion, and migration. Furthermore, HCG18 overexpression inhibited miR-146a-5p and upregulated TRAF6 and p65 expression. Finally, miR-146a-5p/TRAF6 was found to be involved in the role of HCG18 in GC progression in vivo. Altogether, HCG18 promotes GC progression via the miR-146a-5p/TRAF6 axis and could be a GC treatment target.