DiGeorge Syndrome Critical Region Gene 5 Research Articles

The role of long noncoding RNA DGCR5 in cancers: Focus on molecular targets.

Long noncoding RNAs (lncRNAs) are major components of cellular transcripts that are emerging as important players in various biological pathways. Due to their specific expression and functional diversity in a variety of cancers, lncRNAs have promising applications in cancer diagnosis, prognosis, and therapy. Studies have shown that lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) with high specificity and accuracy has the potential to become biomarkers in cancers. LncRNA DGCR5 can be noninvasively extracted from body fluids, tissues, and cells, and can be used as independent or auxiliary biomarkers to improve the accuracy of diagnosis or prognosis. Now, the underlying mechanisms of lncRNAs such as DGCR5 were explored as therapeutic targets, which have been investigated in clinical trials of several cancers. The DGCR5 lacks an appropriate animal model, which is necessary to gain greater knowledge of their functions. While some studies on the uses of DGCR5 have been carried out, the small sample size makes them unreliable. In this review, we presented a compilation of recent publications addressing the potential of lncRNA DGCR5 that could be considered as biomarkers or therapeutic targets, with the hopes of providing promised implications for future cancer therapy.

DGCR5 is Activated by PAX5 and Promotes Pancreatic Cancer via Targeting miR-3163/TOP2A and Activating Wnt/β-Catenin Pathway

Background: DiGeorge syndrome critical region gene 5 (DGCR5) has been shown to be associated with cancer development. However, the biological role and molecular mechanism of DGCR5 in pancreatic cancer (PC) remains largely unknown. Methods: qRT-PCR and fluorescence in situ hybridization was performed to investigate the correlation between DGCR5 expression and prognosis and clinicopathologic characteristics of PC patients. The effects of DGCR5 on PC were studied by gain & loss-of-function experiments in vitro and in vivo. RNA sequencing, bioinformatics analyses, dual-luciferase assays, chromatin immunoprecipitation assay and rescue experiments provided insights into the underlying competing endogenous RNA (ceRNA) mechanism network of DGCR5 in promoting PC progression. Results: DGCR5 was highly expressed in PC tissues compared with adjacent normal tissues and its high expression was associated with poor prognosis in PC patients. Furthermore, DGCR5 depletion inhibited the proliferation, migration and invasion by increasing apoptosis and inducing G0/G1 cell cycle arrest in vitro. Moreover, xenograft assay validated that DGCR5 promotes PC tumor growth in vivo. Mechanistically, DGCR5 was found to act as a ceRNA by sponging miR-3163 to regulate TOP2A and inhibit Wnt/β-catenin pathway. In addition, we found that DGCR5 downregulation could enhance the sensitivity of PC cells to gemcitabine, and ChIP assay showed that the transcription factor PAX5 could bind to the DGCR5 promoter and increase its transcription. Conclusions: Our study demonstrates that DGCR5 is activated by PAX5 and promotes PC progression by sponging miR-3163 to regulate TOP2A and activating wnt/β-catenin pathway, suggesting that DGCR5 may be a potential diagnostic and therapeutic target for PC.

LncRNA DGCR5 Isoform-1 Silencing Suppresses the Malignant Phenotype of Clear Cell Renal Cell Carcinoma via miR-211-5p/Snail Signal Axis.

Long non-coding RNAs (lncRNAs) play important roles during the initiation and progression of cancer. We identified DiGeorge Syndrome Critical Region Gene 5 (DGCR5) as a clear cell renal cell carcinoma (ccRCC) cancer- and lineage-specific lncRNA. Agarose gel electrophoresis analysis and sanger sequencing verified two main isoforms of DGCR5 in ccRCC patient tissues and cell lines. Quantitative polymerase chain reaction further demonstrated that the expression level of DGCR5 major isoform (isoform-1) was higher in ccRCC tissues than that in papillary/chromophobe RCC and other multiple solid malignant tumors. We investigate the biological functions of DGCR5 isoform-1 in ccRCC and show that DGCR5 isoform-1 exerts a tumor-promoting effect in ccRCC. DGCR5 isoform-1 is localized in cytoplasm and shares the same binding sequence to the tumor-suppressive miR-211-5p with the epithelial-to-mesenchymal transition key component SNAI. Furthermore, cellular and molecular experiments demonstrate that DGCR5 isoform-1 could sequester miR-211-5p, leading to the elevation of Snail protein and downregulation of its downstream targets and further promoting ccRCC cell proliferation and migration. Thus, our study indicates that DGCR5 isoform-1 could contribute to ccRCC progression by sponging miR-211-5p through regulating the expression of Snail protein and could serve as a reliable diagnostic biomarker in ccRCC.

Long noncoding RNA DGCR5 involves in tumorigenesis of esophageal squamous cell carcinoma via SRSF1-mediated alternative splicing of Mcl-1

Long noncoding RNAs (lncRNAs) emerge as essential roles in the regulation of alternative splicing (AS) in various malignancies. Serine- and arginine-rich splicing factor 1 (SRSF1)-mediated AS events are the most important molecular hallmarks in cancer. Nevertheless, the biological mechanism underlying tumorigenesis of lncRNAs correlated with SRSF1 in esophageal squamous cell carcinoma (ESCC) remains elusive. In this study, we found that lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) was upregulated in ESCC clinical samples, which associated with poor prognosis. Through RNA interference and overexpression approaches, we confirmed that DGCR5 contributed to promote ESCC cell proliferation, migration, and invasion while inhibited apoptosis in vitro. Mechanistically, DGCR5 could directly bind with SRSF1 to increase its stability and thus stimulate alternative splicing events. Furthermore, we clarified that SRSF1 regulated the aberrant splicing of myeloid cell leukemia-1 (Mcl-1) and initiated a significant Mcl-1L (antiapoptotic) isoform switch, which contributed to the expression of the full length of Mcl-1. Moreover, the cell-derived xenograft (CDX) model was validated that DGCR5 could facilitate the tumorigenesis of ESCC in vivo. Collectively, our findings identified that the key biological role of lncRNA DGCR5 in alternative splicing regulation and emphasized DGCR5 as a potential biomarker and therapeutic target for ESCC.

Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling.

(1) Background: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is an intractable problem for many clinical oncologists. The mechanisms of resistance to EGFR-TKIs are complex. Long non-coding RNAs (lncRNAs) may play an important role in cancer development and metastasis. However, the biological process between lncRNAs and drug resistance to EGFR-mutated lung cancer remains largely unknown. (2) Methods: Osimertinib- and afatinib-resistant EGFR-mutated lung cancer cells were established using a stepwise method. A microarray analysis of non-coding and coding RNAs was performed using parental and resistant EGFR-mutant non-small cell lung cancer (NSCLC) cells and evaluated by bioinformatics analysis through medical-industrial collaboration. (3) Results: Colorectal neoplasia differentially expressed (CRNDE) and DiGeorge syndrome critical region gene 5 (DGCR5) lncRNAs were highly expressed in EGFR-TKI-resistant cells by microarray analysis. RNA-protein binding analysis revealed eukaryotic translation initiation factor 4A3 (eIF4A3) bound in an overlapping manner to CRNDE and DGCR5. The CRNDE downregulates the expression of eIF4A3, mucin 1 (MUC1), and phospho-EGFR. Inhibition of CRNDE activated the eIF4A3/MUC1/EGFR signaling pathway and apoptotic activity, and restored sensitivity to EGFR-TKIs. (4) Conclusions: The results showed that CRNDE is associated with the development of resistance to EGFR-TKIs. CRNDE may be a novel therapeutic target to conquer EGFR-mutant NSCLC.

DGCR5 is activated by PAX5 and promotes pancreatic cancer via targeting miR-3163/TOP2A and activating Wnt/β-catenin pathway.

Long noncoding RNA DiGeorge syndrome critical region gene 5 (DGCR5) has been shown to be highly associated with cancer development. However, the biological role and molecular mechanism of DGCR5 in pancreatic cancer (PC) remains largely unknown. This study aimed to explore the role of DGCR5 in PC. It was revealed that DGCR5 was highly expressed in PC tissues compared with adjacent normal tissues and was associated with poor prognosis in PC patients. Furthermore, DGCR5 depletion inhibited the proliferation, migration and invasion by increasing apoptosis and inducing G0/G1 cell cycle arrest in vitro. Moreover, xenograft assay validated that DGCR5 promotes PC tumor growth in vivo. Mechanistically, DGCR5 was found to act as a ceRNA by sponging miR-3163 to regulate DNA topoisomerase 2-alpha (TOP2A) and inhibit Wnt/β-catenin pathway. In addition, it was found that DGCR5 downregulation could enhance the sensitivity of PC cells to gemcitabine, and ChIP assay showed that PAX5 (Paired Box 5) could bind to the promoter region of DGCR5 and increase its transcription. The results of the present study indicated that DGCR5 may be a potential diagnostic biomarker and therapeutic target for PC.

LncRNA DGCR5 Up-Regulates TGF-β1, Increases Cancer Cell Stemness and Predicts Survival of Prostate Cancer Patients.

BackgroundLong non-coding RNA (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) plays different roles in different types of human cancer, but its role in prostate cancer (PC) has not been reported.MethodsDGCR5 and TGF-β1 expression in paired tumor and adjacent healthy tissues from 64 PC patients was analyzed by performing RT-qPCR. A 5-year follow-up study was performed to analyze the prognostic value of DGCR5 for PC. The interaction between DGCR5 and TGF-β1 was analyzed by overexpression experiments. Cell stemness was analyzed by cell stemness assay.ResultsIn our study, we found that DGCR5 was down-regulated in tumor tissues than in adjacent healthy tissues of PC patients, but TGF-β1 was up-regulated in the tumor tissues. DGCR5 expression was not affected by clinical stages, but low DGCR5 level in the tumor was correlated with poor survival. DGCR5 and TGF-β1 were inversely correlated in tumor tissues but not in adjacent healthy tissues. DGCR5 over-expression resulted in down-regulation of TGF-β1, while TGF-β1 treatment did not significantly affect DGCR5 expression. DGCR5 over-expression led to decreased stemness of PC cells, but TGF-β1 treatment played a reverse role and attenuated the effects of DGCR5 over-expression. DGCR5 may decrease the stemness of PC cells by down-regulating TGF-β1.

LncRNA DGCR5 promotes non-small cell lung cancer progression via sponging miR-218-5p.

Non-small cell lung cancer (NSCLC) is one of the most ordinary malignant tumors worldwide. Recent researches have proved that long noncoding RNAs (lncRNAs) play vital roles in many diseases. The aim of this study was to investigate the exact function of lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) in the development of NSCLC. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect DGCR5 expression in paired NSCLC patients' tissue samples and cell lines. The function of DGCR5 in NSCLC was detected through wound healing assay and transwell assay in vitro. Besides, mechanism assays were conducted to observe the interaction between DGCR5 and microRNA-218-5p (miR-218-5p). DGCR5 was remarkably highly expressed in NSCLC tissues compared to that of adjacent normal tissues. The migration and invasion of NSCLC cells were significantly promoted via overexpression of DGCR5. However, the silence of DGCR5 significantly inhibited NSCLC cell migration and invasion. Moreover, RT-qPCR results revealed that miR-218-5p was down-regulated via overexpression of DGCR5, while miR-218-5p was up-regulated after the knockdown of DGCR5. Further experiments showed that miR-218-5p was a direct target of DGCR5 in NSCLC. DGCR5 enhances NSCLC cell migration and invasion via targeting miR-218-5p, indicating that DGCR5 may be a potential therapeutic target in NSCLC.

Retracted:Propofol exerts anticancer activity on hepatocellular carcinoma cells by raising lncRNA DGCR5

Hepatocellular carcinoma is one of the most fatal cancers worldwide. Propofol is an intravenous anesthetic extensively used in clinical. Herein, we tested the anticancer activity of propofol on hepatocellular carcinoma, along with the internal molecular mechanism related to lncRNA DiGeorge syndrome critical region gene 5 (DGCR5). Followed by propofol stimulation, hepatocellular carcinoma Huh-7 and HepG2 cell viability, proliferation, migration, invasion, and apoptosis were tested, respectively. Then, DGCR5 expression levels in hepatocellular carcinoma tissues and cells were measured. sh-DGCR5 was transfected to silence DGCR5 expression. Subsequently, the influence of DGCR5 silence on propofol caused Huh-7 and HepG2 cell viability loss, proliferation inhibition, migration and invasion suppression, apoptosis induction, as well as Raf1/ERK1/2 and Wnt/β-catenin pathways inactivation were assessed, respectively. We discovered that propofol declined Huh-7 and HepG2 cell viability, proliferation, migration and invasion, but increased cell apoptosis. DGCR5 had a relatively lower expression level in hepatocellular carcinoma tissues and cells. Propofol elevated DGCR5 expression in Huh-7 and HepG2 cells. Increased expression of DGCR5 was connected with the anticancer activity of propofol on Huh-7 and HepG2 cells. Besides, propofol repressed Raf1/ERK1/2 and Wnt/β-catenin pathways through elevating DGCR5 expression. In conclusion, the anticancer activity of propofol on hepatocellular carcinoma was verified in this study. Propofol repressed hepatocellular carcinoma Huh-7 and HepG2 cell growth and metastasis at least by elevating DGCR5 and hereafter inactivating Raf1/ERK1/2 and Wnt/β-catenin pathways.

LncRNA DGCR5 inhibits the proliferation of colorectal cancer cells by downregulating miR-21.

Long non-coding RNA (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) serves roles as a tumor suppressor or oncogene in different types of cancer. The current study aimed to explore the role of DGCR5 in colorectal cancer (CRC). It was revealed that the expression of DGCR5 was downregulated, while microRNA (miR)-21 was upregulated in CRC. The expression level of DGCR5 in tumor tissue decreased, while expression levels of miR-21 increased, with advancing stages of the disease. The expression levels of DGCR5 and miR-21 were inversely associated in tumor tissues. In CRC cells in vitro, miR-21 overexpression failed to significantly affect DGCR5, while DGCR5 overexpression resulted in reduced expression levels of miR-21. DGCR5 overexpression showed no significant effects on cancer cell migration and invasion, but suppressed cancer cell proliferation in vitro. miR-21 overexpression increased cancer cell proliferation and attenuated the effects of DGCR5 overexpression. Therefore, lncRNA DGCR5 may inhibit the proliferation of CRC cells by downregulating miR-21.

LncRNA DGCR5 regulates the non-small cell lung cancer cell growth, migration, and invasion through regulating miR-211-5p/EPHB6 axis.

Non-small cell lung cancer (NSCLC) accounts for about 80% of lung cancers worldwide. In recent years, importance of noncoding RNAs including long noncoding RNA and microRNA in regulating tumor progression has been appreciated. Abnormally expression of DiGeorge syndrome critical region gene 5 (DGCR5) was found in multiple human cancers but its function in NSCLC is largely unknown. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to explore DGCR5 expression level in NSCLC. Bioinformatic analyses were conducted to explore the targets of DGCR5. Cell counting kit-8 assay, wound-healing assay, and transwell invasion assay were performed to analyze functions of DGCR5. RT-qPCR revealed that DGCR5 expression in NSCLC cells was significantly lower than in normal cell. DGCR5 overexpression suppresses NSCLC cell growth, migration, and invasion. Online algorithms found EPH receptor B6 (EPHB6) and DGCR5 contains same miR-211-5p binding region. The predicted connections were further validated by luciferase activity reporter assay. Recue experiments showed DGCR5 regulates NSCLC cell behaviors via targeting miR-211-5p/EPHB6. These findings collectively identified DGCR5/miR-211-5p/EPHB6 triple axis in NSCLC, which may novel understanding regarding the tumorigenesis of NSCLC.

DGCR5 promotes cancer stem cell-like properties of radioresistant laryngeal carcinoma cells by sponging miR-506 via Wnt pathway.

Cancer stem cells (CSCs) have been recognized as the significant cause of tumor recurrence. Long noncoding RNAs (lncRNAs) are involved in various cancers, including human laryngeal cancer. So far the correlation between lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) and CSC-like properties in human laryngeal cancer remains barely known. In our current study, two human larynx squamous carcinoma cell lines (Hep-2 and Hep-2R) with different radio sensitivities were cultured. Interestingly, CSC-like phenotypes were much more enriched in Hep-2R cells. We found that DGCR5 was upregulated and microRNA-506 (miR-506) was downregulated in Hep-2R cells. In addition, silence of DGCR5 could inhibit the stemness and enhance the radiosensitivity of Hep-2R cells. Meanwhile, overexpression of miR-506 also suppressed the CSC-like traits and the radiosensitivity was increased significantly. In addition, miR-506 was predicted as target of DGCR5 and the correlation between them was validated in our study. Finally, we observed that Wnt pathway exerted a significant role in human laryngeal CSCs and DGCR5 inhibition could repress Wnt signaling activity by sponging miR-506. In vivo assays were performed and we found that DCGR5 depressed stemness of human laryngeal cancer cells through modulating miR-506 and Wnt signaling pathway. Taken these together, we reported that DGCR5 induced CSC-like properties by sponging miR-506 through activating Wnt in human laryngeal carcinoma cells.

Polydatin protects H9c2 cells from hypoxia-induced injury via up-regulating long non-coding RNA DGCR5.

Polydatin (PD), a monocrystalline polyphenolic drug mainly found in the roots of Polygonum cuspidatum, has various pharmacological activities. Long non-coding RNAs (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) was found to participate in the suppression of multiple cancers. Here, we proposed to study the effect of PD on myocardial infarction (MI) by inducing DGCR5. CCK-8 assay was performed to detect the viability of H9c2 cells. Flow cytometry was utilized to test apoptosis of H9c2 cells. These results determined the optimal concentration and effect time of hypoxia as well as PD. Si-DGCR5 was transfected into cells and the expression level was determined by qRT-PCR. Western blot was utilized to evaluate the expression of apoptosis-related proteins, Bcl-2, Bax, and cleaved-caspase-3, as well as autophagy-associated proteins including Beclin-1, p62, and LC3-II/LC3-I. As a result, PD efficiently attenuated hypoxia-induced apoptosis and autophagy in H9c2 cells. The expression of DGCR5 was down-regulated by hypoxia and up-regulated by PD. Besides, knocking-down the expression of DGCR5 inhibited the protection of PD in H9c2 cells. In addition, PD up-regulated the accumulation of DGCR5, DGCR5 decreased the expression of Bcl-2 and p62, raised the expression of Bax and cleaved-caspase-3, and the proportion of LC3-II/LC3-I. PD stimulated the PI3K/AKT/mTOR and MEK/ERK signaling pathways via up-regulating the expression of DGCR5. Our data demonstrated that PD reduced cell apoptosis and autophagy induced by hypoxia in cardiomyocytes. Moreover, PD activated PI3K/AKT/mTOR and MEK/ERK signaling pathways by up-regulating the expression of DGCR5.

Knockdown of DGCR5 enhances the radiosensitivity of human laryngeal carcinoma cells via inducing miR-195.

Long noncoding RNAs (lncRNAs) exert critical roles in the development of various cancers, including human laryngeal cancer. Radioresistance contributes to the predominant causes of laryngeal cancer recurrence after radiotherapy. The aim of our study was to investigate the association of dysregulated lncRNA and radiation resistance in human larynx squamous carcinoma. Here, we investigated the biological roles of lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) in radioresistance of human laryngeal cancer. Two human larynx squamous carcinoma cell lines (Hep-2 and Hep-2R), with different radiosensitivities in vitro were used in the present study. We observed that DGCR5 was significantly upregulated in Hep-2R cells. Inhibition of DGCR5 by LV-shDGCR5 transfection restrained Hep-2R cell proliferation and sensitized cells to radiation. Reversely, overexpression of DGCR5 exhibited an opposite phenomenon in vitro. In addition, microRNA (miR)-195 was predicted as a direct downstream target of DGCR5. Dual-luciferase reporter and RNA immunoprecipitation assays verified the direct interaction between them. Meanwhile, miR-195 was observed to be reduced in Hep-2R cells and miR-195 mimics repressed Hep-2 cell growth. Moreover, radiosensitivity of Hep-2R cells was greatly enhanced by overexpression of miR-195, which could be reversed by upregulation of DGCR5. Finally, in vivo experiments were used to validate that knockdown of DGCR5 suppressed laryngeal carcinoma via targeting miR-195. In conclusion, we indicated that DGCR5 could contribute to the radioresistance of human laryngeal carcinoma cells via sponging miR-195.

Long noncoding RNA DGCR5 suppresses gastric cancer progression by acting as a competing endogenous RNA of PTEN and BTG1.

Long noncoding RNA (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) has been reported to correlate with a variety of cancers, with its expression pattern and potential mechanism not clarified in gastric cancer (GC). In this study, we demonstrated that DGCR5 was downregulated in cancerous tissues and plasma samples frompatients with GC, and its downregulation was associated with advanced TNM stage and positive lymphatic metastasis. Plasma DGCR5 had an area under the receiver operating characteristic curve (AUC) of 0.722 for diagnosis of GC. Gain- and loss-of-function of DGCR5 revealed that DGCR5 functioned as a competing endogenous RNA for miR-23b to suppress GC cell proliferation, invasion and migration, and facilitate apoptosis by regulating PTEN and BTG1 in vitro. Furthermore, the overexpression of DGCR5 suppressed tumor growth, and inhibited the expression of miR-23b and proliferation antigen Ki-67, but increased the expression of PTEN and BTG1 in vivo. In conclusion, our results show that DGCR5 is a tumor-suppressive lncRNA that regulates PTEN and BTG1 expression through directly binding to miR-23b. This mechanism may contribute to a better understanding of GC pathogenesis and provide a potential therapeutic strategy for GC.

LncRNA DGCR5 acts as a tumor suppressor in papillary thyroid carcinoma via sequestering miR-2861.

A vast amount of evidence indicates that long non-coding RNAs (lncRNAs) are involved in cancer. Previous studies have indicated that lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) is aberrantly expressed in lung cancer, pancreatic ductal adenocarcinoma and hepatocellular carcinoma. However, the role of DGCR5 in papillary thyroid carcinoma (PTC) has remained elusive. In the present study, it was revealed that DGCR5 was significantly downregulated in PTC tissues compared with that in adjacent normal tissues. Through functional experiments, it was demonstrated that ectopic overexpression of DGCR5 markedly suppressed PTC cell growth and invasion. A bioinformatics analysis suggested that DGCR5 binds to microRNA (miR)-2861. A total of 5 putative binding sites for miR-2861 were identified in DGCR5, and a luciferase reporter assay confirmed the direct interaction between DGCR5 and miR-2861. Furthermore, reverse transcription-quantitative polymerase chain reaction analysis indicated that ectopic overexpression of DGCR5 led to a decreased expression of miR-2861 in PTC cells and miR-2861 mimic transfection caused a downregulation of DGCR5. miR-2861 level was upregulated in PTC tissues compared with adjacent tissues and negatively correlated with DGCR5 level. In addition, rescue experiments indicated that ectopic expression of miR-2861 reversed the effects of DGCR5 overexpression on PTC cell proliferation and invasion. Taken together, the present results demonstrated that DGCR5 inhibits PTC progression via sponging miR-2861, indicating DGCR5 may serve as a therapeutic target.

Upregulation of lncRNA DGCR5 correlates with better prognosis and inhibits bladder cancer progression via transcriptionally facilitating P21 expression.

Mounting studies show that long noncoding RNAs (lncRNAs) could affect human cancer progression, including bladder cancer (BCa). LncRNA DiGeorge syndrome critical region gene 5 (DGCR5) has been proven to be involved in lung cancer, pancreatic ductal adenocarcinoma, and hepatocellular carcinoma. However, the function of DGCR5 in BCa remains largely unknown. Here, we found that DGCR5 expression was significantly downregulated in BCa tissues compared with adjacent normal tissues. Higher expression of DGCR5 predicted higher survival rate in BCa patients. Functional experiments indicated that DGCR5 overexpression markedly inhibited that proliferation, colony formation, and cell-cycle progression in BCa cells. Furthermore, ectopic expression of DGCR5 led to decreased BCa cell migration, invasion, and epithelial-mesenchymal transition while promoting apoptosis. In vivo xenograft assay also illustrated that DGCR5 overexpression inhibited BCa growth. In the mechanism, we found that DGCR5 interacted with AT-rich interaction domain 1A (ARID1A), a chromatin remodeling protein, to promote P21 transcription. Knockdown of P21 could significantly rescue the suppressed proliferation, migration, and invasion of BCa cells by DGCR5 overexpression. In summary, our study demonstrated that DGCR5 transcriptionally promotes P21 expression to suppress BCa progression.

Long noncoding RNA DGCR5 represses hepatocellular carcinoma progression by inactivating Wnt signaling pathway.

Increasing studies have indicated that long noncoding RNAs (lncRNAs) exert important roles in hepatocellular carcinoma (HCC). Therefore, it is of great significance to identify the dysregulated lncRNAs in HCC. According to the previous reports, it has been suggested that DiGeorge syndrome critical region gene 5 (DGCR5) might participate in HCC and can serve as potential biomarker for HCC. In our current study, we concentrated on the biological function and roles of lncRNA-DGCR5 in HCC. It was indicated that DGCR5 was decreased in HCC tissues and HCC cells including HepG2, Hep3B, MHCC-97L, SNU-449, and SNU-182 cells compared with the normal human liver cell line LO2. Overexpression of DGCR5 was able to restrain HCC growth, migration, and invasion capacity in HepG2 and SNU-449 cells. In addition, whether lncRNA-DGCR5 can regulate Wnt/β-catenin pathway during HCC progression is unclear. In our study, it was found that upregulation of DGCR5 inactivated Wnt signaling pathway through inhibiting β-catenin, cyclin D1 and increasing GSK-3β levels. Subsequently, in vivo tumor xenografts were established using HepG2 cells to investigate the function of DGCR5 in HCC development. Inconsistent with the in vitro findings, increase of DGCR5 dramatically suppressed HCC tumor progression in vivo. Taken these together, it was uncovered in our research that DGCR5 could play tumor suppressive role by targeting Wnt signaling in HCC progression.

LncRNA DGCR5 represses the development of hepatocellular carcinoma by targeting the miR-346/KLF14 axis.

Long non-coding RNAs (lncRNAs) are a class of regulatory noncoding RNAs. Emerging evidence highlights the critical roles of lncRNAs in the progression of hepatocellular carcinoma (HCC). Although many lncRNAs have been identified in the development of HCC, the association between DiGeorge syndrome critical region gene 5 (DGCR5) and HCC remains unclear. In the current study, we focused on the biological role of DGCR5 in HCC. We observed that DGCR5 was decreased in HCC cells, including SMCC7721, Hep3B, HepG2, MHCC-97L, MHCC-97H, and SNU449 hepatocellular carcinoma cells, compared with the normal human liver cell line THLE-3 normal human liver cells. In addition, DGCR5 overexpression could repress HCC cell growth, migration, and invasion considerably. Increasing studies have indicated the interactions between lncRNAs and microRNAs. MicroRNAs are endogenous small noncoding RNAs and they can play important roles in tumorigenesis. MicroRNA 346 (miR-346) has been demonstrated in various human cancer types, including HCC. MiR-346 was found to be increased in HCC cells and DGCR5 can act as a sponge of miR-346 to modulate the progression of HCC. The binding correlation between DGCR5 and miR-346 was validated in our research. Subsequently, Krüppel-like factor 14 (KLF14) was predicted as a downstream target of miR-346 and miR-346 can induce the development of HCC by inhibiting KLF14. Finally, we proved that DGCR5 can rescue the inhibited levels of KLF14 repressed by miR-346 mimics in MHCC-97H and Hep3B cells. Taken together, it was indicated in our study that DGCR5 can restrain the progression of HCC through sponging miR-346 and modulating KLF14 in vitro.

The effects of aberrant expression of LncRNA DGCR5/miR‐873‐5p/TUSC3 in lung cancer cell progression

Lung cancer is the most common cause of cancer‐related mortality worldwide, and nonsmall cell lung cancer (NSCLC) accounts for 80% of all pulmonary carcinomas. Recently, long noncoding RNAs (lncRNAs) have been paid attention for exploring treatment of various diseases. Upregulation of DiGeorge syndrome critical region gene 5 (DGCR5) predicts better lung squamous cell carcinoma prognosis; therefore, we explore the role of DGCR5 in lung cancer in our present study. Consecutive patients with LC were treated in our hospital between January 2015 and January 2016. qRT‐PCR demonstrated that DGCR5 was significantly lower in neoplastic tissues than in non‐neoplastic tissues. For in vitro experiments, cell growth, migration, and invasion were significantly lower in A549 cells transfected with pcDNA3.1‐DGCR5 than pcDNA3.1, which were verified by 5‐diphenyltetrazolium bromide (MTT) assay, scratch test, and transwell assay, respectively, with no significant induction on cell apoptosis that was demonstrated by flow cytometry (FCM) assay. Bioinformatics analysis predicted that 3’ untranslated region (UTR) of tumor suppressor candidate 3 (TUSC3, 49‐55 bp) and DGCR5 (801‐807 bp) shared a common hsa‐miR‐873‐5p binding site, and the direct interaction between DGCR5 and hsa‐miR‐873‐5p or hsa‐miR‐873‐5p and TUSC3 was verified by dual‐luciferase reporter assay. qRT‐PCR demonstrated that hsa‐miR‐873‐5p was dramatically higher and TUSC3 was significantly lower in neoplastic tissues than in non‐neoplastic tissues. DGCR5 decreased the protein level of TUSC3 by miR‐873‐5p which was demonstrated by Western blot and immunofluorescence. The role of DGCR5 in tumorigenesis in vivo was consistent with in vitro assays, Ki‐67‐positive cell number (exhibited by immunohistochemical staining), tumor size, and tumor weight of A549‐DGCR5 group were significantly lower in comparison with A549‐control group.