CASC19: An Oncogenic Long Non-coding RNA in Different Cancers.

A 324 bp lncRNA called CASC19 is found on chromosome 8q24.21. Recent research works have revealed that CASC19 is involved in the prognosis of tumors and related to the regulation of the radiation tolerance mechanisms during tumor radiotherapy (RT). This review sheds light on the changes and roles that CASC19 plays in many tumors and diseases, such as nasopharyngeal carcinoma (NPC), cervical cancer, colorectal cancer (CRC), non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (ccRCC), gastric cancer (GC), pancreatic cancer (PC), hepatocellular carcinoma (HCC), glioma, and osteoarthritis (OA). CASC19 provides a new strategy for targeted therapy, and the regulatory networks of CASC19 expression levels play a key role in the occurrence and development of tumors and diseases. In addition, the expression level of CASC19 has predictive roles in the prognosis of some tumors and diseases, which has major implications for clinical diagnoses and treatments. CASC19 is also unique in that it is a key gene affecting the efficacy of RT in many tumors, and its expression level plays a decisive role in improving the success rate of treatments. Further research is required to determine the precise process by which CASC19 causes changes in diseased cells in some tumors and diseases.

LncRNA CASC19: a novel oncogene involved in human cancer

Multiple studies have shown that long non-coding RNAs (lncRNAs) play an important role in the occurrence and development of diverse cancers. Cancer susceptibility candidate 19 (CASC19), encoded by chromosome 8q24.21, is a newly discovered lncRNA that contains 324 nucleotides. CASC19 has been found to be significantly overexpressed in different human cancers, such as non-small cell lung carcinoma, gastric cancer, colorectal cancer, pancreatic cancer, clear cell renal cell carcinoma, glioma, cervical cancer, and nasopharyngeal carcinoma. Moreover, dysregulation of CASC19 was closely associated with clinicopathological parameters and cancer progression. CASC19 regulates a variety of cell phenotypes, including cell proliferation, apoptosis, cell cycle, migration, invasion, epithelial–mesenchymal transition, autophagy, and therapeutic resistance. In this study, we review recent studies on the characteristics and biological function of CASC19, as well as its role in human cancers. These findings suggest that CASC19 may be both a reliable biomarker and a potential therapeutic target in cancers (AU)

LncRNA CASC19: a novel oncogene involved in human cancer.

Multiple studies have shown that long non-coding RNAs (lncRNAs) play an important role in the occurrence and development of diverse cancers. Cancer susceptibility candidate 19 (CASC19), encoded by chromosome 8q24.21, is a newly discovered lncRNA that contains 324 nucleotides. CASC19 has been found to be significantly overexpressed in different human cancers, such as non-small cell lung carcinoma, gastric cancer, colorectal cancer, pancreatic cancer, clear cell renal cell carcinoma, glioma, cervical cancer, and nasopharyngeal carcinoma. Moreover, dysregulation of CASC19 was closely associated with clinicopathological parameters and cancer progression. CASC19 regulates a variety of cell phenotypes, including cell proliferation, apoptosis, cell cycle, migration, invasion, epithelial-mesenchymal transition, autophagy, and therapeutic resistance. In this study, we review recent studies on the characteristics and biological function of CASC19, as well as its role in human cancers. These findings suggest that CASC19 may be both a reliable biomarker and a potential therapeutic target in cancers.

LncRNA CASC19 Enhances the Radioresistance of Nasopharyngeal Carcinoma by Regulating the miR-340-3p/FKBP5 Axis.

Radioresistance remains a serious obstacle encountered in the radiotherapy of nasopharyngeal carcinoma (NPC). Both mRNAs and non-coding RNAs (ncRNAs), including long ncRNA (lncRNA) and microRNA (miRNA), play essential roles in radiosensitivity. However, the comprehensive expression profiles and competing endogenous RNA (ceRNA) regulatory networks among lncRNAs, miRNAs, and mRNAs in NPC radioresistance are still bewildering. In this study, we performed an RNA-sequencing (RNA-seq) assay in the radioresistant NPC cells CNE2R and its parental cells CNE2 to identify the differentially expressed lncRNAs, miRNAs, and mRNAs. The ceRNA networks containing lncRNAs, miRNAs, and mRNAs were predicted on the basis of the Pearson correlation coefficients and authoritative miRanda databases. In accordance with bioinformatic analysis of the data of the tandem mass tag (TMT) assay of CNE2R and CNE2 cells and the gene chip assay of radioresistant NPC samples in pre- and post-radiotherapy, the radioresistance-related signaling network of lncRNA CASC19, miR-340-3p, and FKBP5 was screened and further verified using an RT-qPCR assay. CASC19 was positively associated with FKBP5 expression while negatively correlated with miR-340-3p, and the target binding sites of CASC19/miR-340-3p and miR-340-3p/FKBP5 were confirmed using a dual-luciferase reporter assay. Moreover, using an mRFP-GFP-LC3 maker, it was found that autophagy contributed to the radioresistance of NPC. MiR-340-3p inhibition or FKBP5 overexpression could rescue the suppression of autophagy and radioresistance induced by CASC19 knockdown in CNE2R cells. In conclusion, the CASC19/miR-340-3p/FKBP5 network may be instrumental in regulating NPC radioresistance by enhancing autophagy, which provides potential new therapeutic targets for NPC.

Overexpression of CASC19 contributes to tumor progression and predicts poor prognosis after radical resection in hepatocellular carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been implicated as functional molecules in hepatocellular carcinoma (HCC) progression. The present research aimed to investigate the levels of LncRNA cancer susceptibility candidate gene 19 (CASC19) in HCC tissues and cell lines and to explore its potential role in the diagnosis and prognosis of HCC. METHODS: HCC tissues and cell lines were collected to assess the levels of CASC19 by real-time quantitative reverse transcription PCR (RT-qPCR). The prognostic value of CASC19 was evaluated using the Kaplan-Meier method and Cox regression analysis. The functional role of CASC19 in regulating HCC cell proliferation, migration, and invasion was evaluated by Cell Counting Kit-8 (CCK-8) and Transwell analysis. The potential targeted miR-140-5p of CASC19 was confirmed by a dual-luciferase reporter assay. RESULTS: High CASC19 expression positively correlated with tumor size, differentiation, and TNM stage in HCC patients (P < 0.05). Patients with high CASC19 expression have a poorer survival prognosis and are prone to relapse compared to those with low CASC19. miR-140-5p, a target miRNA for CASC19, negatively correlated with CASC19 levels in tumor tissues. Reduced CASC19 levels attenuated cell proliferation, migration, and invasion, but this attenuation was reversed by suppression of miR-140-5p. CONCLUSION: Up-regulated CASC19 may serve as a biomarker for predicting poor prognosis in HCC patients. In vitro, overexpressed CASC19 promoted the progression of HCC, indicating that CASC19 may be a possible therapeutic target for the treatment of HCC.

LncRNA CASC19 accelerates chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis.

BACKGROUND: Osteoarthritis (OA) is one kind of degenerative joint disease that happens in articular cartilage and other joint tissues. Long non-coding RNAs (lncRNAs) have been reported to serve as pivotal regulators in many diseases, including OA. However, the role and relevant regulatory mechanisms of CASC19 in OA remain unknown. METHODS: The expression levels of CASC19, miR-152-3p, and DDX6 were identified by reverse-transcription polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. The relationship between miR-152-3p and CASC19 or DDX6 was predicted by bioinformatics tools and verified by the dual-luciferase reporter assay. RESULTS: CASC19 was verified to exhibit higher expression in OA tissues and cells. Moreover, inhibition of CASC19 weakened proinflammatory cytokine (IL-6, IL-8, and TNF-α) production and cell apoptosis but facilitated cell viability. Experiments of the ceRNA mechanism elucidated that miR-152-3p was a sponge for CASC19, and miR-152-3p targeted DDX6, suggesting that CASC19 sponged miR-152-3p to release DDX6. Finally, results from rescue assays proved that the impacts of CASC19 silencing on chondrocytes apoptosis and proinflammatory cytokine production could be reversed by DDX6 overexpression. CONCLUSIONS: It was concluded that lncRNA CASC19 accelerated chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis. These findings may offer an effective biological target for OA treatment.

lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway.

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.

Long non­coding RNA CASC19 promotes glioma progression by modulating the miR­454­3p/RAB5A axis and is associated with unfavorable MRI features.

Glioma is one of the most common malignancies of the nervous system. Long non­coding RNAs (lncRNAs) are regulators involved in the progression of tumors. The present study aimed to determine the role of lncRNA cancer susceptibility 19 (CASC19) in glioma and its underlying molecular mechanism. Reverse transcription­quantitative PCR was performed to detect CASC19 and microRNA (miR)­454­3p expression in glioma and normal brain tissues. Ras­related protein in brain 5A (RAB5A) expression in glioma cells was also analyzed via western blotting. The relationship between CASC19 expression, clinicopathological parameters and MRI characteristics in patients with glioma was analyzed. Cell Counting Kit­8, BrdU, wound healing and Transwell assays were adopted to detect glioma cell proliferation, migration and invasion, respectively. The dual­luciferase reporter gene and RNA immunoprecipitation experiments were conducted to verify the targeting relationship between CASC19 and miR­454­3p, and between miR­454­3p and RAB5A. The results revealed that CASC19 expression was significantly upregulated in glioma tissues and cell lines. CASC19 expression was also positively associated with tumor diameter and pathological grade. Additionally, its high expression was closely associated with tumor MRI signal heterogeneity and peritumoral edema. CASC19 upregulation promoted glioma cell proliferation and metastasis, while CASC19­knockdown demonstrated the opposite effect. CASC19 sponged miR­454­3p, which indirectly increased RAB5A expression. The results demonstrated that the CASC19/miR­454­3p/RAB5A axis is involved in the promotion of glioma progression.

Long non-coding RNA CASC19 facilitates non-small cell lung cancer cell proliferation and metastasis by targeting the miR-301b-3p/LDLR axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a lethal tumor resulting in a large number of cancer-related deaths globally. Long noncoding RNAs (lncRNAs) may modulate tumor initiation and metastasis. Although dysregulation of lncRNA cancer susceptibility 19 (CASC19) is validated in NSCLC, further exploration of the CASC19-regulated mechanism in NSCLC is still needed. METHODS: CASC19 expression was examined in NSCLC cells by a quantitative reverse transcriptase-polymerase chain reaction. The specific role of CASC19 in NSCLC was analyzed by cell counting kit-8, EdU, Transwell and western blot assays. The interaction between miR-301b-3p and CASC19 or low-density lipoprotein receptor (LDLR) was confirmed by luciferase reporter and RNA immunoprecipitation assays. RESULTS: CASC19 is markedly overexpressed in NSCLC. Its deficiency impairs cell proliferation, as well as metastasis in NSCLC. Molecular mechanism experiments indicated that CASC19 negatively modulates the expression of miR-301b-3p and miR-301b-3p can bind with CASC19 in NSCLC. In addition, miR-301b-3p binds to LDLR to impair its expression in NSCLC. Finally, rescue experiments showed that miR-301b-3p inhibition or LDLR overexpression counteracted the CASC19 knockdown-mediated function on cell proliferation and metastasis in NSCLC. CONCLUSIONS: CASC19 facilitates NSCLC cell proliferation and metastasis by targeting the miR-301b-3p/LDLR axis, offering a possible strategy for lncRNA-targeted treatment in NSCLC.

Overexpression of CASC19 indicates poor prognosis and facilitates proliferation, migration and invasion in colorectal cancer.

BACKGROUND: Recent studies reveal lncRNAs are associated with tumor progression or metastasis in colorectal cancer (CRC). However, the functional roles of lncRNAs in colorectal liver metastases (CRLM) are still poorly understood. In this study, we performed an integrative analysis of long noncoding RNAs (lncRNAs) of CRLM in Chinese population. METHODS: We first applied RNA-seq and Short Time-series Expression Miner (STEM) to identify differentially expressed lncRNAs in normal tissues, tumor tissues and matched liver metastasis tissues in discovery cohort including four patients with CRLM, and subsequently differentially expressed lncRNAs were checked in the validation cohort consisting of 21 patients with CRLM by qRT-PCR. Then we analyzed the association between lncRNAs and overall survival (OS) in the third cohort with 108 CRC patients. Finally, we investigated the function of lncRNAs in HCT-116 and LoVo cell lines. RESULTS: RNA-seq and STEM analysis identified four lncRNAs (HL-5, HL-20, HL-38, and HL-59) according with the expression trend of N (normal tissues) < T (tumor tissues) < M (matched liver metastasis tissue), which may be associated with CRLM. Univariate analyses showed that high CASC19 expression was associated with poorer prognosis (P=0.013). CASC19 knockdown inhibited cell migration more than 50% in LoVo cells and HCT-116 cells (P<0.001), and significantly decreased cell invasion (P<0.001), as determined with the Matrigel assays. In contrast, cell invasion and migration were increased when CASC19 was overexpressed in HCT-116 and LoVo cells (P<0.001). CONCLUSIONS: Our results showed that liver metastasis tissues and primary tissues of CRC had different expression profiles of lncRNAs. We suggest that CASC19 is a promising biomarker for CRC patients.