LncRNA HOTAIR is a Prognostic Biomarker for the Proliferation and Chemoresistance of Colorectal Cancer via MiR-203a-3p-Mediated Wnt/ß-Catenin Signaling Pathway.

HOX transcript antisense RNA (HOTAIR) plays a vital role in carcinogenesis. However, its functional and regulatory roles remain unclear. In this study, we aimed to investigate its biological function and clinical significance in human colorectal cancer (CRC). We examined the expression levels of lncRNA HOTAIR and miR-203a-3p in CRC tissues and CRC cell lines by qRT-PCR. Gain and loss-of-function assays were performed to examine the effects of HOTAIR and miR-203a-3p on the proliferation and chemoresistance of CRC cells. The possible mechanisms of HOTAIR were also explored by fluorescence reporter assay and Western blot. The expressions of HOTAIR were upregulated in CRC tissue tissues compared to adjacent control tissues. We also found HOTAIR was downregulated by miR-203a-3p in CRC cell lines. Both HOTAIR knockdown and miR-203a-3p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that β-catenin and GRG5 were inhibitory targets of miR-203a-3p, and that Wnt/β-catenin signaling was inhibited by both HOTAIR knockdown and miR-203a-3p overexpression. Significantly, we found that increased expression of miR-203a-3p is essential for cell proliferation repression, chemoresistance reduction, and Wnt/β-catenin signaling inhibition induced by HOTAIR knockdown. Our study demonstrated that the lncRNA HOTAIR could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-203a-3p and the activity of Wnt/β-catenin signaling pathway.

Xiao Z ，Qu Z ，Chen Z ，Fang Z ，Zhou K ，Huang Z ，Guo X ，Zhang Y ... -  《-》

The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling.

Han P ，Li JW ，Zhang BM ，Lv JC ，Li YM ，Gu XY ，Yu ZW ，Jia YH ，Bai XF ，Li L ，Liu YL ，Cui BB ... -  《Molecular Cancer》

A novel long non-coding RNA XLOC_004787, is associated with migration and promotes cancer cell proliferation by downregulating mir-203a-3p in gastric cancer.

Miao R ，Yao Z ，Hu B ，Jin T ，Zhu D ，Shi Y ，Gong Y ，Shao S ，Shao C ... -  《BMC GASTROENTEROLOGY》

Knockdown of long non-coding RNA HOTAIR inhibits cisplatin resistance of gastric cancer cells through inhibiting the PI3K/Akt and Wnt/β-catenin signaling pathways by up-regulating miR-34a.

HOX transcript antisense RNA (HOTAIR), a well-known long non-coding RNA (lncRNA), has been reported to be related to cisplatin (DDP) resistance in gastric cancers. However, the molecular mechanism of HOTAIR in DDP resistance of gastric cancer (GC) remains largely undefined. The aim of this study was to investigate the role and underlying mechanism of HOTAIR in regulating cisplatin resistance of GC. The results showed that HOTAIR was over-expressed in GC tissues and GC cell lines, while miR-34a was low-expressed. Luciferase reporter assay and RIP assay proved that HOTAIR directly bound to miR-34a. MiR-34a expression was significantly increased in si-HOTAIR-transfected cells. Anti-miR-34a reversed the effect of si-HOTAIR on the DDP resistance, apoptosis-related genes, PI3K/Akt and Wnt/β-catenin signaling pathways in DDP-resistant GC cells, indicating that the effects of HOTAIR are dependent on miR-34a. In addition, knockdown of HOTAIR enhanced DDP inhibitory effect on tumor growth in vivo. In conclusion, HOTAIR knockdown inhibited DDP resistance of gastric cancer cells by upregulating miR-34a. The effect of HOTAIR/miR-34a axis on GC cells may be involved in the PI3K/Akt and Wnt/β-catenin signaling pathways. The results indicated that HOTAIR might be a new potential target in GC therapy.

Cheng C ，Qin Y ，Zhi Q ，Wang J ，Qin C ... -  《-》

The Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Progression by Competitively Binding miR-217 with TCF7L2 and Enhancing the Wnt/β-Catenin Signaling Pathway.

The long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) contributes to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer remains unknown. In the present study, we investigated whether CRNDE was involved in the development of colorectal cancer via the binding of microRNA (miR)-217 with transcription factor 7-like 2 (TCF7L2) to enhance the Wnt signaling pathway. Quantitative polymerase chain reaction was used to detect CRNDE, miR-217 and TCF7L2 in colorectal cancer tissues and cells. The CCK-8 assay, wound healing assay, and Transwell assay were used to detect cell proliferation, migration and invasion, respectively. Western blotting and luciferase activity assays were used to identify CRNDE and TCF7L2 as one of the direct targets of miR-217. The activity of the Wnt/β-catenin signaling pathway was analyzed by the TOPflash assay, and the subcellular localization of β-catenin and TCF7L2 was analyzed by western blotting and confocal microscopy. In this study, we found that high expression of CRNDE is negatively correlated with low expression of miR-217 in colorectal cancer tissue and colorectal cancer cells. The dual luciferase reporter analysis showed that miR-217 is bound to CRNDE and TCF7L2 and negatively regulate their expression. CRNDE down-regulation inhibited the cell proliferation, migration and invasion in vitro and in vivo and the inhibitions were both completely blocked after miR-217 inhibition or TCF7L2 overexpression. Finally, TOPflash analysis showed that the activity of Wnt/β-catenin signaling is inhibited by CRNDE down-regulation and rescued by TCF7L2 over-expression. Consistently immunostaining and western blotting analysis showed that the expression of b-catenin and TCF7L2 in the nucleus was significantly decreased by CRNDE down-regulation and was rescued by TCF7L2 over-expression. The present study suggest that CRNDE involves in the cell proliferation, migration and invasion of colorectal cancer cells via increasing the expression of TCF7L2 and activity of Wnt/β-catenin signaling through binding miR-217 competitively.

Yu B ，Ye X ，Du Q ，Zhu B ，Zhai Q ，Li XX ... -  《-》