With the development of functional genomics studies, a mass of long non‐coding RNAs (LncRNA) were discovered from the human genome. Long non‐coding RNAs serve as pivotal regulators of genes that are able to generate LncRNA–binding protein complexes to modulate a great number of genes. Recently, the LncRNA urothelial carcinoma‐associated 1 (UCA1) has been revealed to be dysregulated, which plays a critical role in the development of a few cancers. However, the role of the biology and clinical significance of UCA1 in the tumorigenesis of oral squamous cell carcinoma (OSCC) remain unknown. We found that UCA1 expression levels were upregulated aberrantly in tongue squamous cell carcinoma tissues and associated with lymph node metastasis and TNM stage. We explored the expression, function, and molecular mechanism of LncRNA UCA1 in OSCC. In the present work, we revealed that UCA1 silencing suppressed proliferation and metastasis and induced apoptosis of OSCC cell lines in vitro and in vivo, which might be related to the activation level of the WNT/β‐catenin signaling pathway. Our research results emphasize the pivotal role of UCA1 in the oncogenesis of OSCC and reveal a novel LncRNA UCA1–β‐catenin–WNT signaling pathway regulatory network that could contribute to our understanding in the pathogenesis of OSCC and assist in the discovery of a viable LncRNA‐directed diagnostic and therapeutic strategy for this fatal disease.

Background Achaete scute-like 2 (Ascl2), a basic helix-loop-helix (bHLH) transcription factor, controls the fate of intestinal stem cells. However, the role of Ascl2 in colon cancer progenitor cells remains unknown. The cell line HT-29 (47.5–95% of CD133 + population) and LS174T (0.45% of CD133 + population) were chosen for functional evaluation of Ascl2 in colon cancer progenitor cells after gene knockdown by RNA interference. Methodology/Principal Findings Immunohistochemistry demonstrated that Ascl2 was significantly increased in colorectal adenocarcinomas. Downregulation of Ascl2 using RNA interference in cultured colonic adenocarcinoma HT-29 and LS174T cells reduced cellular proliferation, colony-forming ability, invasion and migration in vitro, and resulted in the growth arrest of tumor xenografts in vivo. The Ascl2 protein level in CD133 + HT-29 cells was significantly higher than in CD133 − HT-29 cells. Ascl2 blockade via shRNA interference in HT-29 cells (shRNA-Ascl2/HT-29 cells) resulted in 26.2% of cells staining CD133 + compared with 54.7% in control shRNA-Ctr/HT-29 cells. The levels of ‘stemness’ associated genes, such as CD133, Sox2, Oct4, Lgr5, Bmi1, and C-myc, were significantly decreased in shRNA-Ascl2/HT-29 and shRNA-Ascl2/LS174T cells in vitro as well as in the corresponding tumor xenograft (CD133 was not performed in shRNA-Ascl2/LS174T cells). The shRNA-Ascl2/HT-29 cells had inhibited abilities to form tumorspheres compared with control. The microRNA (miRNAs) microarrays, identified 26 up-regulated miRNAs and 58 down-regulated miRNAs in shRNA-Ascl2/HT-29 cells. Expression levels of let-7b, miRNA-124, miRNA-125b, miRNA-17, miRNA-20a and miRNA-302b, involved in the regulation of ‘stemness’, were quantified with qPCR, which confirmed their identities. Restoration of miRNA-302b, via its mimic, led to the restoration of shRNA-Ascl2/HT-29 ‘stemness’ characteristics, including tumorsphere formation and ‘stemness’ associated genes levels, and the recovery of cellular behaviors, including colony-forming ability, invasion and migration in vitro. Conclusions/Significance Ascl2 may be a potential target for the inhibition of colon cancer progenitor cells, and functions through a miR-302b-related mechanism.

SOX2 and Hath1 are inversely expressed in gastric carcinoma. SOX2 provides a survival advantage to patients of gastric carcinoma and appears to be associated with metastasis and clinical stages.