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This study aimed to investigate the role of the MIR210 host gene (MIR210HG), a long noncoding RNA (lncRNA), in the proliferation of colon cancer cells and its potential mechanism involving the ferroptosis pathway. We assessed MIR210HG expression in colon cancer cell lines and tissues, and examined the effects of its overexpression and knockdown on cell proliferation. Proteomic analysis was conducted to explore the interaction between MIR210HG and ferroptosis pathway components. The binding of MIR210HG to poly(rC) binding protein 1 (PCBP1) was predicted using catRAPID and confirmed through RNA pull-down and RNA immunoprecipitation (RIP) experiments. MIR210HG was significantly upregulated in colon cancer cells and tissues. Its overexpression promoted, while its knockdown inhibited, colon cancer cell proliferation. MIR210HG was found to be associated with ferroptosis pathway components and to bind to PCBP1, which was experimentally validated. The inhibition of ferroptosis by MIR210HG through PCBP1 binding was confirmed, highlighting its role in promoting cell proliferation. MIR210HG promotes colon cancer cell proliferation by binding to PCBP1 and inhibiting ferroptosis. These findings suggest MIR210HG as a potential therapeutic target for colon cancer. [ABSTRACT FROM AUTHOR]

Hypoxic pulmonary hypertension (HPH) is a pathophysiological syndrome in which pulmonary vascular pressure increases under hypoxic stimulation and there is an urgent need to develop emerging therapies for the treatment of HPH. LncRNA MIR210HG is a long non-coding RNA closely related to hypoxia and has been widely reported in a variety of tumor diseases. But its mechanism in hypoxic pulmonary hypertension is not clear. In this study, we identified for the first time the potential effect of MIR210HG on disease progression in HPH. Furthermore, we investigated the underlying mechanism through which elevated levels of MIR210HG promotes the transition from a contractile phenotype to a synthetic phenotype in PASMCs under hypoxia via activation of autophagy-dependent ferroptosis pathway. While overexpression of HIF-2α in PASMCs under hypoxia significantly reversed the phenotypic changes induced by MIR210HG knockdown. We further investigated the potential positive regulatory relationship between STAT3 and the transcription of MIR210HG in PASMCs under hypoxic conditions. In addition, we established both in vivo and in vitro models of HPH to validate the differential expression of specific markers associated with hypoxia. Our findings suggest a potential mechanism of LncRNA MIR210HG in the progression of HPH and offer potential targets for disease intervention and treatment. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14–16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood. [ABSTRACT FROM AUTHOR]

Abstract Hepatocellular carcinoma (HCC) is a major cause of cancer-related death due to early metastasis or recurrence. Tumor angiogenesis plays an essential role in the tumorigenesis of HCC. Accumulated studies have validated the crucial role of lncRNAs in tumor angiogenesis. Here, we established an angiogenesis-related multi-lncRNAs risk model based on the machine learning for HCC prognosis prediction. Firstly, a total of 348 differential expression angiogenesis-related lncRNAs were identified by correlation analysis. Then, 20 of these lncRNAs were selected through univariate cox analysis and used for in-depth study of machine learning. After 1,000 random sampling cycles calculating by random forest algorithm, four lncRNAs were found to be highly associated with HCC prognosis, namely LUCAT1, AC010761.1, AC006504.7 and MIR210HG. Subsequently, the results from both the training and validation sets revealed that the four lncRNAs-based risk model was suitable for predicting HCC recurrence. Moreover, the infiltration of macrophages and CD8 T cells were shown to be closely associated with risk score and promotion of immune escape. The reliability of this model was validated by exploring the biological functions of lncRNA MIR210HG in HCC cells. The results showed that MIR210HG silence inhibited HCC growth and migration through upregulating PFKFB4 and SPAG4. Taken together, this angiogenesis-related risk model could serve as a reliable and promising tool to predict the prognosis of HCC.

Chronic hypoxia in the renal tubular interstitium has been reported to contribute to the progression of chronic kidney disease. Recently, long‐noncoding RNAs have been shown to be involved in various pathological conditions, including hypoxia, one of which is the MIR210 host gene (MIR210HG). To elucidate the function of MIR210HG in renal hypoxia, we exposed primary cultured renal proximal tubular epithelial cells to hypoxia and examined the temporal profile of MIR210HG expression and the role of MIR210HG interaction with hypoxia‐inducible factor1α (HIF1α, encoded by HIF1A). MIR210HG expression was induced by hypoxia. HIF1A silencing and cobalt chloride exposure showed that MIR210HG expression in hypoxia is HIF1α‐dependent. MIR210HG silencing significantly reduced both the mRNA and protein levels of HIF1α, pointing to positive feedback regulation. To further investigate the details of this regulation, we turned to the in‐silico miRNA targets of MIR210HG. We found that miR‐93‐5p levels increased when MIR210HG was knocked down. We then showed that miR‐93‐5p reduced the expression of HIF1A mRNA and MIR210HG. Furthermore, a dual luciferase assay confirmed that miR‐93‐5p binds to MIR210HG and HIF1A 3′ UTR, inhibiting their expression. In conclusion, the long‐noncoding RNA MIR210HG is induced shortly after hypoxia, and it promotes HIF1α expression by competing for miR‐93‐5p and inhibiting it. MIR210HG plays a crucial role in the biological response to hypoxia in renal tubular epithelial cells. [ABSTRACT FROM AUTHOR]

Cisplatin is one of the most effective chemotherapeutic agents strongly associated with nephrotoxicity. Tubular adult renal progenitor cells (tARPC) can regenerate functional tubules and participate in the repair processes after cisplatin exposition. This study investigated the molecular mechanisms underlying the protective effect of tARPC on renal epithelium during cisplatin nephrotoxicity. By performing a whole-genome transcriptomic analysis, we found that tARPC, in presence of cisplatin, can strongly influence the gene expression of renal proximal tubular cell [RPTEC] by inducing overexpression of CYP1B1, a member of the cytochrome P450 superfamily capable of metabolizing cisplatin and of hypoxia/cancer-related lncRNAs as MIR210HG and LINC00511. Particularly, tARPC exerted renoprotection and regeneration effects via extracellular vesicles (EV) enriched with CYP1B1 and miR-27b-3p, a well-known CYP1B1 regulatory miRNA. The expression of CYP1B1 by tARPC was confirmed by analyzing biopsies of cisplatin-treated renal carcinoma patients that showed the colocalization of CYP1B1 with the tARPC marker CD133. CYP1B1 was also overexpressed in urinary EV purified from oncologic patients that presented nephrotoxicity episodes after cisplatin treatment. Interestingly CYP1B1 expression significantly correlated with creatinine and eGFR levels. Taken together, our results show that tARPC are able to counteract cisplatin-induced nephrotoxicity via CYP1B1 release through EV. These findings provide a promising therapeutic strategy for nephrotoxicity risk assessment that could be related to abundance of renal progenitors. [ABSTRACT FROM AUTHOR]

Abstract Background Breast cancer is the most common cancer in women around the world, and the molecular mechanisms of breast cancer progression and metastasis are still unclear. This study aims to clarify the function and N6,2′-O-dimethyladenosine (m6A) regulation of lncRNA MIR210HG in breast cancer. Results High expression of MIR210HG was confirmed in breast cancer. MIR210HG promoted breast cancer progression, which was mediated by its encoded miR-210. MIR210HG was regulated by IGF2BP1 mediated m6A modification. IGF2BP1 was confirmed highly expressed in breast cancer and induced both MIR210HG and miR-210 expression, which contributed to breast cancer progression. In addition, MIR210HG transcript was stabilized by IGF2BP1 and co-factor ELAVL1. IGF2BP1 was a direct target of MYCN via E-box binding motif. MYCN induced IGF2BP1 expression in breast cancer cells. MIR210HG and miR-210 expressions were also increased by MYCN. Conclusions In breast cancer, MIR210HG functions as an oncogenic lncRNA, which is also mediated by its encoded miR-210. In addition, both IGF2BP1 and ELAVL1 enhance the stability of MIR210HG, which contributes to the progression of breast cancer. Interestingly, IGF2BP1 is directly activated by MYCN, which explains the oncogenic role of MYCN. These findings clarify the m6A regulation related molecular mechanism of breast cancer progression. The MYCN/IGF2BP1/MIR210HG axis may serve as an alternative molecular mechanism of breast cancer progression.

Long noncoding RNAs (lncRNAs) have evoked considerable interest in recent years due to their critical functions in the regulation of disease processes. Abnormal expression of lncRNAs is found in multiple diseases, and lncRNAs have been exploited for diverse medical applications. The lncRNA MIR210HG is a recently discovered lncRNA that is widely dysregulated in human disease. MIR210HG was described to have biological functions with potential roles in disease development, including cell proliferation, invasion, migration, and energy metabolism. And MIR210HG dysregulation was confirmed to have promising clinical values in disease diagnosis, treatment, and prognosis. In this review, we systematically summarize the expression profiles, roles, underlying mechanisms, and clinical applications of MIR210HG in human disease. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) promotes tumorigenesis and metastasis and increases tumor tolerance to treatment intervention. Abnormal activation of transforming growth factor β (TGF-β) and Wnt pathway induces EMT. Long non-coding RNAs (lncRNAs) significantly influence EMT regulation. Herein, we show that MIR210HG is overexpressed in endometrial cancer tissues, which is associated with poor prognosis. MIR210HG silencing significantly inhibited proliferation, migration, invasion, and EMT phenotype formation in vitro as well as tumorigenesis in vivo. Mechanistically, bioinformatics analyses, RNA binding protein immunoprecipitation (RIP) assays, and luciferase assays showed that MIR210HG acts as a molecular sponge of miR-337-3p and miR-137 to regulate the expression of HMGA2. Additionally, MIR210HG overexpression significantly enriched the Wnt/β-catenin and TGF-β/Smad3 signaling pathway genes, while MIR210HG or HMGA2 knockdown suppressed the Wnt/β-catenin and TGF-β/Smad3 signaling pathway. Our findings on the MIR210HG-miR-337-3p/137-HMGA2 axis illustrate its potential as a target for endometrial cancer therapeutic development.

This study aimed to confirm the expression of the seminal plasma long noncoding RNAs (lncRNAs) microRNA210 host gene (MIR210HG) in varicocele (VC) patients, to further explore the association between MIR210HG and VC severity and to evaluate whether MIR210HG can predict VC‐related dyszoospermia. Semen samples from 188 VC patients and 92 healthy men were collected. Quantitative reverse transcriptase PCR detected seminal plasma MIR210HG levels. Receiver operating characteristic analysis assessed the ability of MIR210HG to screen patients with VC, or to screen VC patients with abnormal semen quality. Logistic analysis assessed the value of MIR210HG in predicting dyszoospermia in VC patients. The levels of MIR210HG in seminal plasma of VC patients were upregulated, which could screen VC patients. In addition, the levels of seminal plasma MIR210HG were upregulated with VC severity and were downregulated at 6 months after surgery in VC patients. Moreover, elevated MIR210HG levels in VC patients with abnormal semen quality could screen patients with abnormal semen quality and could independently predict the occurrence of dyszoospermia in VC patients. Seminal plasma MIR210HG expression is upregulated in VC patients, is associated with the severity of VC and may function as an independent predictor of VC‐related dyszoospermia. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common cancer in women around the world, and the molecular mechanisms of breast cancer progression and metastasis are still unclear. This study aims to clarify the function and N6,2′-O-dimethyladenosine (m6A) regulation of lncRNA MIR210HG in breast cancer. Results: High expression of MIR210HG was confirmed in breast cancer. MIR210HG promoted breast cancer progression, which was mediated by its encoded miR-210. MIR210HG was regulated by IGF2BP1 mediated m6A modification. IGF2BP1 was confirmed highly expressed in breast cancer and induced both MIR210HG and miR-210 expression, which contributed to breast cancer progression. In addition, MIR210HG transcript was stabilized by IGF2BP1 and co-factor ELAVL1. IGF2BP1 was a direct target of MYCN via E-box binding motif. MYCN induced IGF2BP1 expression in breast cancer cells. MIR210HG and miR-210 expressions were also increased by MYCN. Conclusions: In breast cancer, MIR210HG functions as an oncogenic lncRNA, which is also mediated by its encoded miR-210. In addition, both IGF2BP1 and ELAVL1 enhance the stability of MIR210HG, which contributes to the progression of breast cancer. Interestingly, IGF2BP1 is directly activated by MYCN, which explains the oncogenic role of MYCN. These findings clarify the m6A regulation related molecular mechanism of breast cancer progression. The MYCN/IGF2BP1/MIR210HG axis may serve as an alternative molecular mechanism of breast cancer progression. [ABSTRACT FROM AUTHOR]

Background/aims: Colorectal cancer (CRC) is a widespread cancerous disease with an unfavorable prognosis. MIR210HG appears to have a significant connection with the development of CRC, but the precise regulatory mechanism remains obscure., Materials and Methods: Quantitative real-time polymerase chain reaction was utilized to determine expression quantities of MIR210HG and miR-1226-3p. The proliferative capacity of CRC cells was measured by cell counting kit-8. The apoptosis rate of cells was examined using flow cytometry. The invasive capability was assessed through the transwell experiment. The targeted regulation of MIR210HG and miR-1226-3p was validated through dual-luciferase reporter gene experiments., Results: In carcinoma tissues and blood serum of colorectal cancer patients and cell lines, MIR210HG expression was upregulated, while the miR-1226-3p expression was downregulated. MIR210HG had a diagnostic and prognostic value for CRC patients. MIR210HG may target and regulate miR-1226-3p. MIR210HG may have the capacity to augment the vitality and invasion of CRC cells and suppress cell apoptosis, and this influence is counteracted by miR-1226-3p., Conclusion: lncRNA MIR210HG accelerated the progression of colorectal cancer by controlling miR-1226-3p. lncRNA MIR210HG/miR1226-3p may potentially serve as therapeutic targets for addressing colorectal cancer.

The relationship between microRNA (miRNA) and hosting long non-coding RNA (lncRNA) remains unclear. Here, the expression levels of microRNA-210 (miR-210) and hosting lncRNA MIR210HG are significantly increased and positively correlated in gastric cancer (GC). Gain- and loss-of-function studies demonstrate that miR-210 and MIR210HG synergistically promote the migration and invasion of GC cells in vitro. Furthermore, GC sublines simultaneously expressing miR-210 and MIR210HG display synergistic promotion of lung metastasis in vivo. Mechanistically, MIR210HG interacts with DExH-box helicase 9 (DHX9) to increase DHX9/c-Jun complex's occupancy on the promoter of matrix metallopeptidases (MMPs), and thus promotes migration and invasion of GC cells. Additionally, miR-210 directly suppresses the expression of dopamine receptor D5 (DRD5), serine/threonine kinase 24 (STK24) and MAX network transcriptional repressor (MNT), resulting in enhanced migration and invasion. Finally, MYC proto-oncogene (c-Myc) transactivates miR-210 and MIR210HG. Overexpression of miR-210 or/and MIR210HG can rescue the inhibitory effect on the migration and invasion by silencing c-Myc. Moreover, c-Myc inhibitor significantly decreases lung metastasis of GC in vivo. Collectively, our findings identify a novel mechanism, by which c-Myc-activated miR-210 and MIR210HG synergistically promote the metastasis of GC. [ABSTRACT FROM AUTHOR]

An insufficient oxygen supply within the intratumoral environment, also known as hypoxia, induces glioblastoma multiforme (GBM) invasion, stemness, and temozolomide (TMZ) drug resistance. Long noncoding (lnc)RNAs have been reported to be involved in hypoxia and GBM progression. However, their roles in hypoxic GBM malignancy are still unclear. We investigated the mechanisms of hypoxia‐mediated lncRNAs in regulating GBM processes. Using The Cancer Genome Atlas (TCGA) and data mining, hypoxia‐correlated lncRNAs were identified. A hypoxia‐upregulated lncRNA, MIR210HG, locating in nuclear regions, predicted poor prognoses of patients and modulated hypoxia‐promoted glioma stemness, TMZ resistance, and invasion. Depletion of hypoxic MIR210HG suppressed GBM and patient‐derived cell growth and increased TMZ sensitivity in vitro and vivo. Using RNA sequencing and gene set enrichment analysis (GSEA), MIR210HG‐upregulated genes significantly belonged to the targets of octamer transcription factor 1 (OCT1) transcription factor. The direct interaction between OCT1 and MIR210HG was also validated. Two well‐established worse prognostic factors of GBM, insulin‐like growth factor–binding protein 2 (IGFBP2) and fibroblast growth factor receptor 1 (FGFR1), were identified as downstream targets of OCT1 through MIR210HG mediation in hypoxia. Consequently, the lncRNA MIR210HG is upregulated by hypoxia and interacts with OCT1 for modulating hypoxic GBM, leading to poor prognoses. These findings might provide a better understanding in functions of hypoxia/MIR210HG signaling for regulating GBM malignancy. [ABSTRACT FROM AUTHOR]

LncRNA-MIR210HG plays crucial roles in the progression of diverse cancers. However, the expression and function of MIR210HG in ovarian cancer remains unclear. In the present study, we aimed to determine the expression and function of lncRNA-MIR210HG in ovarian cancer under hypoxic conditions. MIR210HG expression in ovarian cancer cells under hypoxic conditions was determined by qPCR analysis, and the distribution was determined by FISH and qPCR analysis based on cell nucleus and cytosol RNA extraction. Epithelial-Mesenchymal Transition (EMT) assay and human umbilical vein endothelial cell-based tube formation and migration assays were employed to determine the potential function of MIR210HG in vitro, followed by establishment of a subcutaneous tumor model in mice. The direct target of MIR210HG was determined by RNA pull-down and western blotting. Furthermore, the expression and clinical correlation of MIR210HG was determined based on malignant tissues from ovarian cancer patients. Our results indicated that MIR210HG was induced by hypoxia, which is HIF-1α dependent and mainly located in the cytosol of ovarian cancer cells. Knockdown of MIR210HG significantly inhibited EMT and tumor angiogenesis in vitro and impaired tumor growth in mice. Molecular investigations indicated that MIR210HG directly targets HIF-1α protein and inhibits VHL-dependent HIF-1α protein degradation in ovarian cancer. Further results demonstrated that MIR210HG was upregulated in ovarian cancer tissues and correlated with tumor progression and poor prognosis of ovarian cancer patients. Our study suggests that hypoxia-induced MIR210HG promotes cancer progression by inhibiting HIF-1α degradation in ovarian cancer, which could be a therapeutic target for ovarian cancer.

LncRNA-MIR210HG plays crucial roles in the progression of diverse cancers. However, the expression and function of MIR210HG in ovarian cancer remains unclear. In the present study, we aimed to determine the expression and function of lncRNA-MIR210HG in ovarian cancer under hypoxic conditions. MIR210HG expression in ovarian cancer cells under hypoxic conditions was determined by qPCR analysis, and the distribution was determined by FISH and qPCR analysis based on cell nucleus and cytosol RNA extraction. Epithelial-Mesenchymal Transition (EMT) assay and human umbilical vein endothelial cell-based tube formation and migration assays were employed to determine the potential function of MIR210HG in vitro , followed by establishment of a subcutaneous tumor model in mice. The direct target of MIR210HG was determined by RNA pull-down and western blotting. Furthermore, the expression and clinical correlation of MIR210HG was determined based on malignant tissues from ovarian cancer patients. Our results indicated that MIR210HG was induced by hypoxia, which is HIF-1α dependent and mainly located in the cytosol of ovarian cancer cells. Knockdown of MIR210HG significantly inhibited EMT and tumor angiogenesis in vitro and impaired tumor growth in mice. Molecular investigations indicated that MIR210HG directly targets HIF-1α protein and inhibits VHL-dependent HIF-1α protein degradation in ovarian cancer. Further results demonstrated that MIR210HG was upregulated in ovarian cancer tissues and correlated with tumor progression and poor prognosis of ovarian cancer patients. Our study suggests that hypoxia-induced MIR210HG promotes cancer progression by inhibiting HIF-1α degradation in ovarian cancer, which could be a therapeutic target for ovarian cancer. [ABSTRACT FROM AUTHOR]

Purpose: Acute kidney injury (AKI) is a serious complication of sepsis and is characterized by inflammatory response. MicroRNA-210 host gene (MIR210HG) is upregulated in human proximal tubular epithelial cells under treatment of inflammatory cytokines. This study aimed to explore the role of MIR210HG in sepsis-induced AKI. Materials and Methods: Cell viability was detected by a cell counting kit 8 assay. The levels of proinflammatory cytokines were detected by enzyme-linked immunosorbent assay kits. The protein levels of p65, IκBα, and p-IκBα were examined by western blot analysis. The nuclear translocation of nuclear factor kappa B (NF-κB) was detected by immunofluorescence assay. The histological changes of kidneys were analyzed by hematoxylin and eosin staining assay. Results: Lipopolysaccharide (LPS) treatment significantly inhibited cell viability and increased productions of proinflammatory cytokines in proximal tubular epithelial cells (HKC-8). Additionally, MIR210HG levels in HKC-8 cells were increased by LPS treatment. MIR210HG silencing inhibited the LPS-induced cell inflammatory response. MIR210HG activated the NF-κB signaling pathway by promoting the phosphorylation of IκBα and nuclear translocation of p65. Rescue assays revealed that the MIR210HGinduced increase of cytokines levels and decline of cell viability were rescued by QNZ treatment. Knockdown of MIR210HG decreased blood urea nitrogen, serum creatinine, and proinflammatory cytokine levels in AKI rats. Moreover, the knockdown of MIR210HG protected against AKI-induced histological changes of kidneys in rats. Conclusion: MIR210HG promotes sepsis-induced inflammatory response of HKC-8 cells by activating the NF-κB signaling pathway. This novel discovery may be helpful for the improvement of sepsis-induced AKI. [ABSTRACT FROM AUTHOR]

BackgroundHypoxia is an important environmental factor and has been correlated with tumor progression, treatment resistance and poor prognosis in many solid tumors, including triple-negative breast cancer (TNBC). Emerging evidence suggests that long noncoding RNA (lncRNA) functions as a critical regulator in tumor biology. However, little is known about the link between hypoxia and lncRNAs in TNBC.MethodsTNBC molecular profiles from The Cancer Genome Atlas (TCGA) were leveraged to identify hypoxia-related molecular alterations. Loss-of-function studies were performed to determine the regulatory role of MIR210HG in tumor glycolysis. The potential functions and mechanisms of hypoxia-MIR210HG axis were explored using qPCR, Western blotting, luciferase reporter assay, and polysome profiling.ResultsWe found that MIR210HG is a hypoxia-induced lncRNA in TNBC. Loss-of-function studies revealed that MIR210HG promoted the Warburg effect as demonstrated by glucose uptake, lactate production and expression of glycolytic components. Mechanistically, MIR210HG potentiated the metabolic transcription factor hypoxia-inducible factor 1α (HIF-1α) translation via directly binding to the 5’-UTR of HIF-1α mRNA, leading to increased HIF-1a protein level, thereby upregulating expression of glycolytic enzymes. MIR210HG knockdown in TNBC cells reduced their glycolytic metabolism and abolished their tumorigenic potential, indicating the glycolysis-dependent oncogenic activity of MIR210HG in TNBC. Moreover, MIR210HG was highly expressed in breast cancer and predicted poor clinical outcome.ConclusionOur results decipher a positive feedback loop between hypoxia and MIR210HG that drive the Warburg effect and suggest that MIR210HG may be a good prognostic marker and therapeutic target for TNBC patients.

Background: Hypoxia is an important environmental factor and has been correlated with tumor progression, treatment resistance and poor prognosis in many solid tumors, including triple-negative breast cancer (TNBC). Emerging evidence suggests that long noncoding RNA (lncRNA) functions as a critical regulator in tumor biology. However, little is known about the link between hypoxia and lncRNAs in TNBC. Methods: TNBC molecular profiles from The Cancer Genome Atlas (TCGA) were leveraged to identify hypoxia-related molecular alterations. Loss-of-function studies were performed to determine the regulatory role of MIR210HG in tumor glycolysis. The potential functions and mechanisms of hypoxia-MIR210HG axis were explored using qPCR, Western blotting, luciferase reporter assay, and polysome profiling. Results: We found that MIR210HG is a hypoxia-induced lncRNA in TNBC. Loss-of-function studies revealed that MIR210HG promoted the Warburg effect as demonstrated by glucose uptake, lactate production and expression of glycolytic components. Mechanistically, MIR210HG potentiated the metabolic transcription factor hypoxia-inducible factor 1α (HIF-1α) translation via directly binding to the 5'-UTR of HIF-1α mRNA, leading to increased HIF-1a protein level, thereby upregulating expression of glycolytic enzymes. MIR210HG knockdown in TNBC cells reduced their glycolytic metabolism and abolished their tumorigenic potential, indicating the glycolysis-dependent oncogenic activity of MIR210HG in TNBC. Moreover, MIR210HG was highly expressed in breast cancer and predicted poor clinical outcome. Conclusion: Our results decipher a positive feedback loop between hypoxia and MIR210HG that drive the Warburg effect and suggest that MIR210HG may be a good prognostic marker and therapeutic target for TNBC patients. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs are involved in the progression of multiple cancers. However, the expression and mechanism of microRNA (miR)210HG in non-small cell lung cancer (NSCLC) remain unclear. Methods: The levels of miR210HG and miR-874 were measured by quantitative real-time polymerase chain reaction in NSCLC tissue samples and cells. Non-small cell lung cancer cell proliferation, migration, and invasion were measured by Cell Counting Kit-8 and transwell assays. Luciferase analysis confirmed the interaction between miR210HG and miR-874. Results: Here, our data showed that miR210HG was overexpressed in NSCLC tissue samples and cells. In vitro functional assays showed that silencing miR210HG blocked NSCLC cell proliferation, migration, and invasion while promoting NSCLC cell radiosensitivity and chemoresistance. Mechanistically, miR-874 was directly regulated by miR210HG. Furthermore, miR-874 expression was reduced in NSCLC tissues and cells. The miR-874 mimic could mitigate the promoting effect of miR210HG on NSCLC cell progression. The data also showed that miR210HG promoted NSCLC cell progression through miR-181a expression by targeting STAT3. Conclusions: Our observations suggest that miR210HG is associated with NSCLC cell progression by regulating the miR-874/STAT3 axis. [ABSTRACT FROM AUTHOR]

Colon cancer is the third most common cancer worldwide, and lymphatic metastasis is one of the principal factors affecting patient prognosis. Recent studies have revealed that long non-coding RNAs (lncRNAs) serve as important regulators in the pathogenesis of colon cancer, therefore affecting patient survival rates. In the present study, colon cancer-associated lncRNAs were screened based on their influence on patient survival. A number of survival-associated lncRNAs (and their potential mechanisms of action) were identified, with the strongest candidate being MIR210HG. Gene expression correlation and protein-protein interaction (PPI) network analyses were performed to identify MIR210HG-associated genes. Various bioinformatics analyses (including gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses) were conducted to investigate the prognostic role of MIR210HG and its associated genes, in colon cancer. Higher expression levels of MIR210HG were associated with shorter overall survival in patients with colon cancer, which was significant in 373 candidates. Multiple findings indicated that MIR210HG may exert its effects in colon cancer through the modulation of energy metabolism and cell adhesion. Further predictions suggested that MIR210HG may affect colon cancer via transcription and post-transcriptional processing. Collectively, these results provided evidence of a transcriptional regulatory network of MIR210HG in colon cancer, and suggested its potential role as a novel biomarker and therapeutic target for colon cancer. [ABSTRACT FROM AUTHOR]

This study aimed to identify potential biomarkers and the therapeutic targets for colorectal adenocarcinoma by systematically evaluate a large scale of long noncoding RNAs (lncRNAs) expression data from TCGA. The algorithm t‐distributed stochastic neighbor embedding and hierarchical clustering were utilized to group the samples into three clusters that showed a different prognosis. To identify the relationship between the clustered groups and different histoclinical features, different statistical methods were used. The functions of LINC01234 and MIR210HG were investigated with the help of the public database. The results showed that the expression levels of lncRNAs were able to distinguish the tumor samples from the normal tissues and in further they were able to predict the prognosis of the patients. We proposed two potential lncRNAs, which might serve as a biomarker or therapeutic targets. LINC01234 can be a good biomarker. In contrast, MIR210HG participated in the progression of colorectal adenocarcinoma by regulating hypoxia. It might function through an lncRNA–microRNA–messenger RNA regulatory network with MIR210 and RASSF7. [ABSTRACT FROM AUTHOR]

Background: In recent years, a large number of studies have shown that differentially expressed lncRNAs are capable of promoting the occurrence and development of tumors by regulating cell proliferation and differentiation. However, the biological effects of lncRNAs in non-small cell lung cancer (NSCLC) are still needed to be further investigated. Methods: The differentially expressed lncRNAs in NSCLC tissues in the downloaded profiles from GEO database were analyzed and further verified in 100 pairs of NSCLC samples collected in our hospital. After identification of the target gene MIR210HG, the relationship between MIR210HG expression and clinical data of NSCLC patients was analyzed. Regulatory effects of MIR210HG on proliferation, migration, and invasion of NSCLC cells were detected by CCK-8, colony formation, and transwell assay, respectively. The binding condition of MIR210HG and DNA methyltransferase 1 (DNMT1) was detected by RNA binding protein immunoprecipitation. Subsequently, chromatin immunoprecipitation assay assessed the promoter binding of DNMT1 to CACNA2D2. Rescue experiments were conducted to assess whether CACNA2D2 can reverse the function of MIR210HG. Results: MIR210HG was highly expressed in NSCLC tissues not only in GSE30219 dataset but also in our collected NSCLC tissues. MIR210HG expression was correlated to tumor stage and lymph node metastasis of NSCLC patients. Besides, lower disease-free survival (DFS) and overall survival (OS) were found in NSCLC patients with high-level MIR210HG compared with those with low-level MIR210HG. Regression analysis indicated that MIR210HG was the independent risk factor for DFS and OS of NSCLC patients. In vitro experiments demonstrated that MIR210HG knockdown remarkably inhibited proliferation and migration of NSCLC cells. MIR210HG could recruit DNMT1, thereafter promoting methylation of CACNA2D2 promoter region. CACNA2D2 overexpression remarkably inhibited cell proliferation. Moreover, inhibited proliferation induced by MIR210HG knockdown was reversed by CACNA2D2 knockdown. Conclusion: MIR210HG can promote the tumorigenesis of NSCLC by inhibiting the expression of CACNA2D2. Our findings provide new therapeutic strategies for the future treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Abstract MIR210HG is a novel long noncoding RNA (lncRNA) and has been found to be overexpresed in osteosarcoma and glioma. However, the level of MIR210HG and its clinical significance in hepatocellular carcinoma (HCC) are not well known. In results of our research, MIR210HG expression was increased in HCC tissue samples and cells compared with paired adjacent normal liver tissue samples and normal liver cell line respectively, and a good marker to discriminate HCC tissues from non-tumorous tissues. MIR210HG high-expression was correlated advanced clinical stage, big tumor size, present vascular invasion and unfavorable histological differentiation. The survival analysis from our cohort and TCGA cohort consistently suggested that HCC patients with MIR210HG high-expression had poorer prognosis than HCC patients with MIR210HG low-expression. Furthermore, univariate and multivariate Cox regression analyses showed that MIR210HG high-expression was an independent unfavorable prognostic factor for overall survival in HCC patients. The in vitro study showed that silencing of MIR210HG depressed HCC cell proliferation, migration and invasion. In conclusion, MIR210HG functions as an oncogenic lncRNA in HCC, and may be a potential biomarker for predicting clinical progression and prognosis. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have been illustrated to function as important regulator in carcinogenesis and cancer progression. However, roles of lncRNA miR210HG (miR210 host gene) in osteosarcoma remain unclear. In this study, miR210HG expression level was significantly upregulated in 55 cases of osteosarcoma tissue samples compared to adjacent normal tissue. Besides, the aberrantly enhanced miR210HG expression predicted poor prognosis and lower survival rate. In vitro, miR210HG knockdown suppressed the osteosarcoma cell proliferation, invasion, and epithelial-mesenchymal transition-related marker (N-cadherin and vimentin) expression. In vivo, miR210HG silencing decreased the tumor growth. miR-503 was verified to be the target miRNA of miR210HG using bioinformatics online program and luciferase assay. Furthermore, miR-503 could reverse the role of miR210HG on osteosarcoma cells. In conclusion, our study indicates that miR210HG sponges miR-503 to facilitate osteosarcoma cell invasion and metastasis, revealing the oncogenic role of miR210HG on osteosarcoma cells. [ABSTRACT FROM AUTHOR]

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play essential roles in various types of cancer, especially the ability of tumor cells to adapt to hypoxia conditions. However, only a few of them have been experimentally validated in cervical squamous cell carcinoma (CSCC). In the current study, we identified a hypoxia-induced lncRNA MIR210HG was excessively expressed in CSCC tissues and regulated by human papillomavirus (HPV) type 16 E6 and E7 via hypoxia-inducible factor 1α (HIF-1α). Functional assays revealed the role of MIR210HG in promoting proliferation, migration and invasion of CSCC cells in vitro under normoxia as well as hypoxia conditions. Meanwhile, stable MIR210HG silencing dramatically repressed tumor growth and pulmonary metastasis in vivo. Mechanistically, the depletion of MIR210HG or HIF-1α decreased each other's expression level, while silencing MIR210HG or HIF-1α respectively downregulated the expression levels of phosphoglycerate kinase 1 (PGK1), one of key metabolic enzymes in the glycolysis pathway. Furthermore, decreased expression of PGK1 by HIF-1α knockdown was reversed through the overexpression of MIR210HG. Also, we demonstrated HIF-1α can activate the transcription of MIR210HG via binding its promoter. Taken together, these results expand our understanding of the cancer-associated functions of hypoxia-induced lncRNAs, and highlight MIR210HG forms a feedback loop with HIF-1α contributing to cervical carcinogenesis, with potential implications for therapeutic targeting., Competing Interests: None., (AJCR Copyright © 2022.)

Objective: Hepatoblastoma is the most common liver tumor. Recent research has found that long non-coding (lnc)RNAs are involved in multiple types of cancers, but the potential mechanism of lncRNA MIR210HG in hepatoblastoma remains unknown. The present study explored the molecular mechanism of MIR210HG in hepatoblastoma progression., Methods: The cell counting kit-8 was used to detect cell viability, and Transwell assays assessed cell migration and invasion. Luciferase reporter assays showed the relationship between MIR210HG and microRNA (miR)-608 and between miR-608 and forkhead box O6 (FOXO6). Functional tests were verified in vivo by a tumor xenograft model. The expression of MIR210HG, miR-608, FOXO6, E-cadherin, N-cadherin, and vimentin was determined by quantitative reverse transcription polymerase chain reaction and western blotting., Results: MIR210HG was shown to be highly expressed in hepatoblastoma tissues and cell lines. Knockdown of MIR210HG reduced proliferation, migration, and invasion in liver cancer cells, and suppressed tumor growth in vivo . MIR210HG competitively combined with miR-608, and miR-608 decreased FOXO6 expression., Conclusion: Our study demonstrated that knockdown of MIR210HG inhibits hepatoblastoma development through binding to miR-608 and downregulating FOXO6. Our results provide novel insights for hepatoblastoma treatment involving the MIR210HG-miR608-FOXO6 axis.

Preeclampsia (PE) is a potentially fatal pregnancy-specific complication. Nevertheless, the pathogenesis of PE remains indistinct. Recently, increasing studies emphasized that long noncoding RNAs (lncRNAs) functions as imperative regulators in PE. The aim of this study was to compare the lncRNAs transcript profile of placentae in early onset severe preeclampsia (EOSP) with lncRNAs in normal pregnancy (NP) and to evaluate the role of lncRNA MIR210HG (microRNA 210 host gene) in the PE pathogenesis. Using RNA sequencing, we compared transcriptome profiles of placentae in EOSP (n = 3) and NP (n = 3). Bioinformatic tools were used to predict the function of differentially expressed genes while qRT-PCR was used to verify RNA sequencing data. The role of MIR210HG in HTR8/SVneo migration and invasion were analyzed by in vitro MIR210HG gene overexpression. Our results showed that 527 lncRNAs and 600 mRNAs were differentially expressed in placental samples of EOSP, and the analysis identified 63 key EOSP related genes. As indicated by bioinformatics analyses, lncRNA MIR210HG was a potential pathogenic marker of PE. LncRNA-MIR210HG expression was upregulated in placental samples of PE and enriched in the canonical Wnt signalling pathway. MiR210HG overexpression inhibited HTR8/SVneo cell migration and invasion in vitro. Additionally, miR210HG upregulated dickkopf-1 expression via the sponging of microRNA-520a-3p (miR-520a-3p), thus repressing trophoblast migration and invasion. Our study showed that MiR210HG is a novel upregulated lncRNA in the placentas of PE and MiR210HG regulates the migration and invasive potential of HTR-8/SVneo cell by targeting the miR-520a-3p/Dickkopf-1 axis. • MiR210HG is over-expressed in preeclampsia placenta tissues. • MiR210HG abrogates the migration/invasion of extravillous trophoblast cell lines (HTR8/SVneo). • MiR210HG is a sponge of MiR-520a-3p and DKK1 is a target of MiR-520a-3p in HTR8/SVneo cells. • MiR210HG suppresses the migration/invasion by regulating MiR-520a-3p/DKK1 axis in HTR8/SVneo cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is one of the most frequent types of cancer world-wide, leading to over 500,000 cancer-related deaths each year. Although many primary colorectal cancer patients can be cured by surgery, up to 60% will develop metastases. Chemotherapeutic strategies are well-established, but finally often lead to chemo-resistance and tumor relapse. A specific chemotherapeutic approach is low dose metronomic (LDM) therapy, which is based on a constant administration of low doses of a chemotherapeutic compound instead of high-dose pulses, which are often a huge burden for patients and also may induce rapid resistance. However, the molecular mechanism of LDM chemotherapy is not fully understood. Our study therefore aims at identifying gene signatures of colorectal cancer progression under LDM chemotherapy which eventually provides new potential biomarkers for therapeutic interventions. Understanding the molecular signatures of colorectal cancer progression under chemotherapeutic treatment will be crucial for the success of future therapy improvements. Here, we used a xenograft-based mouse model to investigate, how whole transcriptome signatures change during metastatic colorectal cancer progression and how such signatures are affected by LDM chemotherapy using RNA sequencing. We characterized mRNAs as well as non-coding RNAs such as microRNAs, long non-coding RNAs and circular RNAs in colorectal-cancer bearing mice with or without LDM chemotherapy. Furthermore, we found that circZNF609 functions as oncogene, since over-expression studies lead to an increased tumor growth while specific knock down results in smaller tumors. Our data represent novel insights into the relevance of non-coding and circRNAs in colorectal cancer and provide a comprehensive resource of gene expression changes in primary tumors and metastases. In addition, we present candidate genes that could be important modulators for successful LDM chemotherapy. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) play important roles in the progression of cervical cancer (CC). However, the roles and underlying molecular mechanisms of lncRNAs in CC remain unclear. In the current study, we discovered a new lncRNA MIR210HG which was upregulated in CC tissues through microarray. The upregulation of MIR210HG was associated with advanced FIGO stage, metastasis, and poor prognosis in CC patients. Function assays showed that MIR210HG inhibition significantly suppressed the proliferation, invasion, and epithelial-mesenchymal transition (EMT) processes in CC and reduced tumor growth in vivo. Mechanistically, we identified that MIR210HG might serve as a competing endogenous RNA (ceRNA) of miR-503-5p to relieve the repressive effect of miR-503-5p on TRAF4 expression in CC cells. In conclusion, we demonstrated that MIR210HG promoted CC progression through regulating the MIR210HG/miR-503-5p/TRAF4 axis, indicating that MIR210HG might act as a novel insight into CC treatment.