Long Non-Coding RNA (lncRNA) X-Inactive Specific Transcript (XIST) Plays a Critical Role in Predicting Clinical Prognosis and Progression of Colorectal Cancer.

BACKGROUND Long non-coding RNAs (lncRNAs) participate in all cancer biology processes of cells. Although functions and associated mechanisms of lncRNAs have been proven in colorectal cancer (CRC), the roles of lncRNA X-inactive specific transcript (XIST) have not been clearly investigated in CRC. MATERIAL AND METHODS Expression of XIST was detected by quantitative real-time PCR (qRT-PCR) assay in CRC cell lines and 196 clinical samples. Correlations between XIST expression and CRC clinicopathological features were analyzed. Log-rank test and Kaplan-Meier test were performed to assess and compare the prognoses of patients with higher and lower expression of XIST. The multivariate Cox regression and univariate Cox regression were conducted to evaluate the risk factors for prognosis of CRC. RESULTS lncRNA XIST was upregulated in CRC cells lines and tissues (p<0.05). Statistical analysis found high XIST expression was correlated with larger tumor size, N1, M1, and topography lymph node metastasis (TNM) III+IV stage of CRC. Moreover, higher expression of XIST could predict poor progression-free survival (PFS) and poor overall survival (OS) of CRC patients. The M1 stage and high expression of XIST were proven to be independent risk factors for poor prognosis (p<0.05). CONCLUSIONS XIST is upregulated in CRC and is significantly correlated with CRC clinical progression. lncRNA XIST overexpression predict poor PFS and poor OS for CRC patients. lncRNA XIST can be an independent risk factor for CRC prognosis, and could be a potential therapeutic target and prognostic biomarker for CRC patients.

Down-regulation of long non-coding RNA HOTAIR inhibits invasion and migration of oesophageal cancer cells via up-regulation of microRNA-204.

Oesophageal cancer is a progressive tumour with high mortality. However, therapies aimed at treating oesophageal cancer remain relatively limited. Accumulating studies have highlighted long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), microRNA-204 (miR-204) and homeobox C8 (HOXC8) in the progression of oesophageal cancer. Herein, we tried to demonstrate the function of HOTAIR, miR-204 and HOXC8 in oesophageal cancer and their relationship. Differentially expressed genes involved in oesophageal cancer were identified. The endogenous expression of HOTAIR and miR-204 in oesophageal cancer cell lines was altered to elucidate their effects and to identify the interaction among HOTAIR, miR-204 and HOXC8. We also explored the underlying regulatory mechanisms of HOTAIR and miR-204 with siRNA against HOTAIR, miR-204 mimic or miR-204 inhibitor. Cell proliferation, migration, invasion and apoptosis were subsequently detected. Xenograft in nude mice was induced to evaluate tumourigenicity. miR-204 was down-regulated, while HOTAIR and HOXC8 were up-regulated in the oesophageal cancer tissues. HOTAIR could competitively bind to miR-204 and miR-204 could further target HOXC8. The oesophageal cancer cells treated with si-HOTAIR or miR-204 mimic exhibited decreased expression levels of HOXC8, Vimentin and MMP-9, but increased E-cadherin level. Silenced HOTAIR or elevated miR-204 inhibited proliferation, migration and invasion, along with stimulated apoptosis of oesophageal cancer cells. In summary, our results show that lncRNA HOTAIR could specifically bind to miR-204 as a competing endogenous RNA and regulate miR-204 and HOXC8. Hence, down-regulation of HOTAIR could inhibit progression of oesophageal cancer, indicating a novel target for oesophageal cancer treatment.