Colorectal cancer is considered as the fourth leading reason of cancer‐linked deaths worldwide. However, our knowledge about its pathogenic mechanism remains inadequate. MicroRNA 32 (miR‐32), a member of small noncoding RNAs, has been found vital roles in tumorigenesis. This study studied its functions and underlying mechanism in colorectal cancer. The experiment revealed the obvious upregulation of miR‐32 in colorectal cancer tissues and six cancer cell lines, compared with normal tissues and cells. Moreover, miR‐32 upregulation reduced cell apoptosis and promoted cell proliferation and migration, while its downregulation displayed opposite effects. Dual luciferase reporter assays proved that miR‐32 bound to the 3′‐untranslated region (3′‐UTR) of OTU domain containing 3 (OTUD3), suggesting that miR‐32 directly targeted OTUD3. Further experiments demonstrated that overexpression of miR‐32 could reduce the expression level of OTUD3. Furthermore, OTUD3 silence promoted proliferation and motility and decreased apoptosis for HCT116 cells and restored partly miR‐32‐mediated cell proliferation, migration, and antiapoptosis for colon cancer. Therefore, our study indicated that miR‐32 enhanced cell proliferation and motility abilities, and inhibited apoptosis by directly targeting OTUD3 in colon cancer cells, which implied that miR‐32 was hopeful to be a biomarker or target used for diagnosis and therapy of colon cancer.
Background
Long noncoding RNA (lncRNA) TUG1 has been reported to display a pivotal role in the tumorigenesis and malignant progression of various types of cancers, including stomach adenocarcinoma (STAD). However, the contribution of aberrant expression of TUG1 and the mechanism by which it serves as a competing endogenous RNA (ceRNA) in STAD remains largely obscure.
Methods
The human STAD cell lines (MGC‐803 and AGS), human normal gastric epithelial cell line (GES‐1), human umbilical vein endothelial cells (HUVECs), and human embryonic kidney cells (HEK293T) were purchased and cultured to investigate the roles of TUG1 in STAD. Twenty BALB/c nude mice were purchased to establish a xenograft model to explore the roles of TUG1 in vivo.
Results
Bioinformatics analysis revealed that TUG1 was upregulated in STAD, of which expression was negatively and positively correlated with miR‐29c‐3p and VEGFA, respectively. Functional analyses indicated that TUG1 functioned as an oncogene to promote malignant behaviors (proliferation, migration, and angiogenesis) of STAD cells; whereas miR‐29c‐3p exerted the opposite role. Mechanistically, the interaction between miR‐29c‐3p with TUG1 and VEGFA was demonstrated. It was observed that miR‐29c‐3p could reverse the TUG1‐induced promotion effect on cell proliferation, migration, and angiogenesis in STAD. Furthermore, TUG1 overexpression promoted STAD cell proliferation, metastasis, and angiogenesis, whereas VEGFA silence restored these effects, both in vitro and in vivo.
Conclusion
This finding confirmed that lncRNA TUG1 acts as a ceRNA for miR‐29c‐3p to promote tumor progression and angiogenesis by upregulating VEGFA, indicating TUG1 as a therapeutic target in STAD management.
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