ABSTRACT
Panax notoginseng saponins (PNS) have recently attracted great attention for their anti-cancer activity in colorectal cancer (CRC). The aim of this study was to explore the functional role and underlying mechanisms of PNS on CRC radiosensitivity. Cell viability was assessed by a Cell Counting kit-8 assay. Cell survival and apoptosis were determined using colony formation assay and flow cytometry, respectively. Quantitative real-time PCR was used to quantify the levels of SNHG6 and miR-137. The targeted correlation between SNHG6 and miR-137 was validated by dual-luciferase reporter and RNA immunoprecipitation assays. Our data supported that PNS weakened the viability of CRC cells. Moreover, PNS promoted the radiosensitivity of CRC cells. Mechanistically, PNS enhanced CRC cell radiosensitivity by upregulating SNHG6. SNHG6 directly targeted miR-137 and inhibited miR-137 expression. MiR-137 was involved in the regulatory effect of SNHG6 on CRC cell radiosensitivity. Furthermore, PNS increased miR-137 expression through SNHG6 in CRC cells. Our study suggested that PNS promoted radiosensitivity in CRC cells at least partly through regulating the SNHG6/miR-137 axis, providing a novel understanding of the anti-cancer mechanism of PNS in CRC.
ABSTRACT
BACKGROUND: Increasing evidence has suggested the involvement of long non-coding RNA taurine upregulated gene 1 (TUG1) in chemoresistance of cancer treatment. However, its function and molecular mechanisms in esophageal squamous cell carcinoma (ESCC) chemoresistance are still not well elucidated. In the present study, we investigate the functional role of TUG1 in cisplatin (DDP) resistance of ESCC and discover the underlying molecular mechanism. RESULTS: Our study revealed that TUG1 was up-regulated in DDP-resistant ESCC tissues and cells. High TUG1 expression was correlated with poor prognosis of ESCC patients. TUG1 knockdown improved the sensitivity of ECA109/DDP and EC9706/DDP cells to DDP. Moreover, TUG1 could epigenetically suppress PDCD4 expression via recruiting enhancer of zeste homolog 2. PDCD4 overexpression could mimic the functional role of down-regulated TUG1 in DDP resistance. PDCD4 knockdown counteracted the inductive effect of TUG1 inhibition on DDP sensitivity of ECA109/DDP and EC9706/DDP cells. Furthermore, TUG1 knockdown facilitated DDP sensitivity of DDP-resistant ESCC cells in vivo. CONCLUSION: TUG1 knockdown overcame DDP resistance of ESCC by epigenetically silencing PDCD4, providing a novel therapeutic target for ESCC.
