Similar Datasets
Project description:Hepatocellular carcinoma (HCC) is the most prevalent liver cancer, characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanism underlying their self-renewal and maintenance are poorly understood. Here we identified a long noncoding RNA (lncRNA) termed HAND2-AS1 that is highly expressed in liver CSCs. Human HAND2-AS1 is highly conserved to its mouse ortholog lncHand2. HAND2-AS1 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanically, HAND2-AS1 recruits the INO80 complex onto BMPR1A promoter to trigger its expression, leading to the activation of BMP signaling. Importantly, targeting HAND2-AS1 by antisense oligonucleotides (ASOs) and BMPR1A by siRNAs have synergistic anti-tumor effects on humanized HCC models. Moreover, knockout of lncHand2 or Bmpr1a in mouse hepatocytes impairs BMP signaling and suppresses the initiation of liver cancer. Our findings reveal that HAND2-AS1 promotes the self-renewal of liver CSCs and drives liver oncogenesis, which may be a potential target for HCC therapy.
2019-02-06 | GSE126122 | GEO
Project description:Investigation the RNA profiling in Huh7 cells upon knock-out lncRNA HAND2-AS1 or knock-down INO80 via gene expression microarray analysis Hepatocellular carcinoma (HCC) is the most prevalent liver cancer, characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanism underlying their self-renewal and maintenance are poorly understood. Here we identified a long noncoding RNA (lncRNA) termed HAND2-AS1 that is highly expressed in liver CSCs. Human HAND2-AS1 is highly conserved to its mouse ortholog lncHand2. HAND2-AS1 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanically, HAND2-AS1 recruits the INO80 complex onto BMPR1A promoter to trigger its expression, leading to the activation of BMP signaling. Importantly, targeting HAND2-AS1 by antisense oligonucleotides (ASOs) and BMPR1A by siRNAs have synergistic anti-tumor effects on humanized HCC models. Moreover, knockout of lncHand2 or Bmpr1a in mouse hepatocytes impairs BMP signaling and suppresses the initiation of liver cancer. Our findings reveal that HAND2-AS1 promotes the self-renewal of liver CSCs and drives liver oncogenesis, which may be a potential target for HCC therapy.
2019-02-06 | GSE126121 | GEO
Project description:LncRNA HAND2-AS1 controls liver cancer stem cell functions and serves as a potential therapy target
| PRJNA521054 | ENA
Project description:LncRNA HAND2-AS1 controls liver cancer stem cell functions and serves as a potential therapy target (RNA microarray)
| PRJNA521056 | ENA
Project description:LncRNA HAND2-AS1 controls liver cancer stem cell functions and serves as a potential therapy target (ChiRP-Seq)
| PRJNA521057 | ENA
Project description:Hepatocellular carcinoma (HCC) is the most prevalent liver cancer, characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanism underlying their self-renewal maintenance is poorly understood. Here, we identified a long noncoding RNA (lncRNA) termed HAND2-AS1 that is highly expressed in liver CSCs. Human HAND2-AS1 and its mouse ortholog lncHand2 display a high level of conservation. HAND2-AS1 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, HAND2-AS1 recruits the INO80 chromatin-remodeling complex to the promoter of BMPR1A, thereby inducing its expression and leading to the activation of BMP signaling. Importantly, interfering with expression of HAND2-AS1 by antisense oligonucleotides (ASOs) and BMPR1A by siRNAs has synergistic anti-tumorigenic effects on humanized HCC models. Moreover, knockout of lncHand2 or Bmpr1a in mouse hepatocytes impairs BMP signaling and suppresses the initiation of liver cancer. Our findings reveal that HAND2-AS1 promotes the self-renewal of liver CSCs and drives liver oncogenesis, offering a potential new target for HCC therapy.
| S-EPMC6717889 | biostudies-literature
Project description:Background: Recent studies have shown that circulating long noncoding RNAs (lncRNAs) could be stably detectable in the blood of cancer patients and play important roles in the diagnosis of many different cancers. However, the value of lncRNAs in the diagnosis of pancreatic cancer (PC) has not been fully explored. Methods: Eleven PC-related lncRNAs were selected by analyzing bioinformatics databases. The expression levels of the lncRNAs were further analyzed in a small set of plasma samples from a training group including 30 noncancer samples (15 healthy and 15 chronic pancreatitis (CP) subjects) and 15 PC samples. Then, the candidate lncRNAs were validated with data from 46 healthy controls, 97 CP patients and 114 PC patients. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the identified lncRNAs. Results: After selection and validation, three characteristic plasma candidate lncRNAs, ABHD11-AS1, LINC00176 and SNHG11, were identified, and their levels were significantly higher in PC patients than in normal controls. We found that among the three candidate lncRNAs, ABHD11-AS1 showed the best diagnostic performance for the detection of PC. Furthermore, ABHD11-AS1 had a higher area under the ROC curve (AUC) than CEA, CA199 and CA125 for early PC diagnosis, while the combination of ABHD11-AS1 and CA199 was more effective than ABHD11-AS1 alone. Conclusions: Plasma ABHD11-AS1 could serve as a potential biomarker for detecting PC, and the combination of ABHD11-AS1 and CA199 was more efficient for the diagnosis of PC than ABHD11-AS1 alone, particularly for early tumor screening.
| S-EPMC6636289 | biostudies-literature
Project description:Background: The lack of obvious symptoms of early gastric cancer (GC) as well as the absence of sensitive and specific biomarkers results in poor clinical outcomes. Tubulin is currently emerging as important regulators of the microtubule cytoskeleton and thus have a strong potential to be implicated in a number of disorders, however, its mechanism of action in gastric cancer is still unclear. Tubulin alpha-1C(TUBA1C) is a subtype of α-tubulin, high TUBA1C expression has been shown to be closely related to a poor prognosis in in various cancers,this study, for the first time, revealed the mechanism of TUBA1C promotes malignant progression of gastric cancer in vitro and in vivo. Methods: The expression of lncRNA EGFR-AS1 was detected in human GC cell lines by qRT–PCR. Mass spectrometry experiments following RNA pulldown assays found that EGFR-AS1 directly binds to TUBA1C, the CCK8, EdU, transwell, wound-healing, cell cycle assays and animal experiments were conducted to investigate the function of TUBA1C in GC. Combined with bioinformatics analyses, reveal interaction between Ki-67, E2F1, PCNA and TUBA1C by western blot. Rescue experiments furtherly demonstrated the relationship of EGFR-AS1and TUBA1C. Results: TUBA1C was proved to be a direct target of EGFR-AS1, TUBA1C promotes gastric cancer proliferation, migration and invasion by accelerating the progression of the cell cycle from the G1 phase to the S phase and activating the expression of oncogenes: Ki-67,E2F1 and PCNA. Conclusions: TUBA1C is a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression and could be a novel biomarker and therapeutic target for GC.
2023-05-10 | PXD040199 | Pride
Project description:Cervical cancer is one of the major malignancies, the pathophysiology and progression of which remain to be scarcely understood. Long non-coding RNAs (lncRNAs) have been previously implicated in the progression of cervical cancer. Here, the purpose of this study was to identify whether lncRNA heart- and neural crest derivative-expressed 2-antisense RNA 1 (HAND2-AS1) affect the development of cervical cancer through regulation of chromosome 16 open reading frame 74 (C16orf74) by mediating a transcription factor E2F4. RT-qPCR was performed to determine the expression of HAND2-AS1 in cervical cancer cells. Then, cervical cancer cells were treated with HAND2-AS1 or si-E2F4 RNA, or C16orf74, after which the proliferation, colony formation, migration and invasion were detected. Moreover, the binding between HAND2-AS1 and E2F4 or between E2F4 and C16orf74 was explored. Finally, the tumorigenesis of cervical cancer cells was measured in nude mice with altered HAND2-AS1/E2F4/C16orf74 expression. HAND2-AS1 exhibited poor expression in cervical cancer, and HAND2-AS1 overexpression suppressed the proliferation, colony formation, migration and invasion of cervical cancer cells. In addition, HAND2-AS1 was found to recruit transcription factor E2F4 to C16orf74 promoter region and down-regulate C16orf74 expression. Lastly, HAND2-AS1/E2F4/C16orf74 modulated the tumorigenesis of cervical cancer in nude mice. In conclusion, this study provided evidence on the inhibitory effect of HAND2-AS1 on the development of cervical cancer through the suppression of C16orf74 expression by recruiting transcription factor E2F4. This study highlights the potential of lncRNA HAND2-AS1 as a target in the treatment of cervical cancer.
| S-EPMC7294116 | biostudies-literature
Project description:Expression level of long non-coding RNA (lncRNA) RHPN1-AS1 in glioma tissues was detected to determine potential risk factors influencing prognosis of glioma. This study aimed to clarify the molecular mechanisms underlying tumorigenesis of glioma and thus to improve therapeutic efficacy of glioma. RHPN1-AS1 levels in glioma tissues (n=105) and normal brain tissues (n=105) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between RHPN1-AS1 level and pathological indicators of glioma patients was analyzed. Glioma patients were followed up for 5 years. Overall survival (OS) and relapse-free survival (RFS) in glioma patients were tested by Kaplan-Meier and log-rank method. Potential factors influencing prognosis of glioma were analyzed by Cox regression model. RHPN1-AS1 was upregulated in glioma tissues. Its level was correlated to histological grade, Karnofsky (KPS) score and postoperative recurrence of glioma patients, rather than sex, age, pathological and tumor size. Glioma patients expressing high level of RHPN1-AS1 suffered worse OS and RFS than those with low level. Advanced histological grade, KPS score <80 and high level of RHPN1-AS1 were considered to be risk factors influencing postoperative prognosis of glioma. High level of RHPN1-AS1 is an independent risk factor for poor prognosis of glioma, which may be utilized as a prognostic hallmark.
| S-EPMC7400277 | biostudies-literature