Background/Aims: 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). Methods: 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. Results: 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. Conclusions: 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.

Here, an RNA‐sequencing assay revealed long noncoding RNAs (lncRNAs) with an ectopic expression between colon cancer (CC) and normal colon epithelial cells, in which lncRNA B4GALT1‐AS1 exhibited the highest change. A 3‐(4,5‐dimethythiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay indicated that B4GALT1‐AS1 knockdown had no effect on CC cell viability, however, cell clone formation analysis showed that B4GALT1‐AS1 knockdown attenuated the capacity of cell clone formation. Additionally, gene set enrichment analysis of this data set revealed that positive enrichment of stem cell‐differentiated signatures and negative embryonic stem cell function and adult tissue stem module were observed in CC cells with B4GALT1‐AS1 knockdown. Furthermore, B4GALT1‐AS1 knockdown suppressed the stemness‐marker expression, the ability of cell spheroid formation, and ALDH1 activity in CC cells. Mechanistically, RNA‐sequencing data found that the Hippo pathway in cancer was shown on pathways mostly upregulated by B4GALT1‐AS1 knockdown, and B4GALT1‐AS1 directly bound to the yes‐associated protein (YAP), a downstream executor of the Hippo pathway, and B4GALT1‐AS1 knockdown promoted the nuclear cytoplasm translocation of YAP and decreased YAP transcriptional activity. Notably, YAP overexpression attenuated the inhibitory effects mediated by B4GALT1‐AS1 knockdown. Our results identify the direct binding of lncRNA B4GALT1‐AS1 to YAP, which is responsible for CC cell stemness.

From the data of this study, biologic mesh had no superiority to synthetic mesh in open inguinal hernia repair with similar recurrence rates and incidence of chronic groin pain, but higher rate of seroma and longer operating time. However, this mesh still needs to be assessed in a large, multicentre, well-designed randomized controlled trial.