Silence of cancer susceptibility candidate 9 inhibits gastric cancer and reverses chemoresistance.
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.
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, 110001, China.|Department of Surgical Oncology, First Affiliated Hospital, China Medical University, Shenyang, 110004, China.
Chao
C
Shang
Department of Gastrointestinal Surgery, Dalian Municipal Central Hospital, Dalian, 116033, China.
Lin
L
Sun
Department of Surgical Oncology, First Affiliated Hospital, China Medical University, Shenyang, 110004, China.
Jiale
J
Zhang
Department of Surgical Oncology, First Affiliated Hospital, China Medical University, Shenyang, 110004, China.
Bochao
B
Zhao
Department of Surgical Oncology, First Affiliated Hospital, China Medical University, Shenyang, 110004, China.
Xiuxiu
X
Chen
Department of Surgical Oncology, First Affiliated Hospital, China Medical University, Shenyang, 110004, China.
Huimian
H
Xu
Department of Surgical Oncology, First Affiliated Hospital, China Medical University, Shenyang, 110004, China.
Baojun
B
Huang
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D062085:RNA, Long Noncoding; C000622084:long noncoding RNA CASC9, human; D004317:Doxorubicin; D017239:Paclitaxel
CASC9; chemotherapy resistance; gastric cancer; long noncoding RNA; malignancy