Silencing long noncoding RNA PVT1 inhibits tumorigenesis and cisplatin resistance of colorectal cancer.

ABSTRACT: Long noncoding RNA plasmacytoma variant translocation 1 (PVT1) plays pivotal roles in tumorigenesis of many cancers, including colorectal cancer (CRC). However, the clinical significance and the biological functions of PVT1 in CRC remain largely unknown. In this study, we found that PVT1 was highly expressed in CRC tissues and cell lines compared with the corresponding non-cancerous samples and normal colon epithelial cells. Clinically, increased expression of PVT1 was positively correlated with tumor size, advanced histological stages, metastases, poor prognosis, and cisplatin resistance of CRC patients. In vitro studies showed that PVT1 silencing inhibited the proliferation, migration, invasion, and apoptosis escape of CRC cells. Knockdown of PVT1 in cisplatin-resistant CRC cells induced proliferation inhibition and apoptosis, whereas overexpression of PVT1 increased proliferation and decreased apoptosis of CRC cells. Mechanically, the levels of drug resistance-associated molecules, including multidrug resistance 1 and multidrug resistance protein 1, as well as the expression of anti-apoptotic Bcl-2 were significantly downregulated whereas the levels of pro-apoptotic Bax and cleaved caspase-3 were increased in PVT1-silenced cisplatin-resistant CRC cells. However, ectopic expression of PVT1 in CRC cells reversed the expressions of the molecules mentioned above. In addition, PVT1 overexpression in CRC cells significantly promoted cisplatin resistance in vivo. Collectively, these results demonstrated that PVT1 is a significant regulator in tumorigenesis and cisplatin resistance of CRC and provided evidence that PVT1 may be a promising target for CRC therapy.

SUBMITTER: Ping G 

PROVIDER: S-EPMC5801353 | biostudies-other | 2018

REPOSITORIES: biostudies-other