Silence of cancer susceptibility candidate 9 inhibits gastric cancer and reverses chemoresistance

Abstract

Cancer Susceptibility Candidate 9 (CASC9) is a novel gene generating long non-coding RNA (lncRNA) with oncogenic potential that was first identified in esophageal cancer. In this study, we have found that CASC9 was overexpressed in gastric cancer (GC) compared to normal gastric tissue. A higher expression level was associated with aggressive pathological characteristics, including deep invasion, poor differentiation and lymph node metastases. In two gastric cancer cell lines, BGC823 and SGC7901, CASC9 were both overexpressed compared to that of normal gastric epithelial cell (GES-1). Moreover, the expression of CASC9 was even higher in BGC823/DR and SGC7901/DR cells that are resistant to paclitaxel or adriamycin. CASC9 knockdown inhibited proliferation and promoted cell apoptosis In BGC823/DR and SGC7901/DR cells. The invasion potential was also significantly inhibited measured by Transwell assay. In addition, CASC9 knockdown in BGC823/DR and SGC7901/DR cells restored chemosensitivity to paclitaxel and adriamycin. This was associated with decreased expression of multidrug resistance 1 (MDR1) protein. Taken together, our data suggest that expression of lncRNA CASC9 correlated with aggressive pathological characteristics of GC, it may serve as a potential oncogene to regulate proliferation, invasion, and chemoresistance of GC cells.

The Long Noncoding RNA Cancer Susceptibility 9 and RNA Binding Protein Heterogeneous Nuclear Ribonucleoprotein L Form a Complex and Coregulate Genes Linked to AKT Signaling

“…For further in‐depth analysis, the lncRNA CASC9 , whose knockdown by three different methods was consistently associated with a loss of cell viability, was selected. The link of CASC9 to viability and proliferation was further supported by data from other tumor entities . We showed that the impact of CASC9 depletion was caused by a mixed phenotype including loss of proliferation and induction of apoptosis.…”

“…We showed that the impact of CASC9 depletion was caused by a mixed phenotype including loss of proliferation and induction of apoptosis. Other studies linked the cellular phenotype of CASC9 to impaired epithelial–mesenchymal transition (EMT) and invasion . However, previously suggested CASC9 target genes involved in EMT, like vimentin, cadherins 1 and 2, and SNAIL family transcriptional repressor 1, were not differentially expressed, which might indicate tumor type–specific differences.…”

Comprehensive bioinformatics analysis identifies lncRNA HCG22 as a migration inhibitor in esophageal squamous cell carcinoma

“…18 Recently, researchers reported that CASC9 could be a predictor of poor prognosis in ESCC. 22,23 Our results confirmed the high expression level of CASC9 in ESCC tumor tissues, and trans-analysis inferred the potential regulatory correlation of CASC9 with MYZAP, a myocardial-related gene. 20,21 CASC9 also plays an oncogene in many other malignancies such as gastric cancer and nasopharyngeal cancer.…”

Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis

“…The patient characteristics are shown in Supplemental Table 1 (supplemental material available online with this article; https://doi.org/10.1172/JCI96218DS1). As shown in Figure 1A, the microarray analysis identified 158 upregulated and 142 downregulated lncRNAs from 7,419 analyzed lncRNAs in the MIBC tissues, including CASC9, MIAT, MEG3, and LINC01133, which are associated with human cancer progression (25)(26)(27)(28). Additionally, one lncRNA (LINC00958, RefSeq accession number NR_038904), Figure 1.…”