The microRNA-381(miR-381)/Spindlin1(SPIN1) axis contributes to cell proliferation and invasion of colorectal cancer cells by regulating the Wnt/β-catenin pathway

Abstract

Our study aimed to investigate the clinical significance and biological functions of Spindlin1 (SPIN1) in colorectal cancer (CRC) tumorigenesis and progression, as well as the mechanism underlying its upregulation. The expression of SPIN1 was detected by immunohistochemistry and western blotting assays. Bioinformatics prediction and dual-luciferase reporter assays were used to determine whether microRNA-381 (miR-381) could target SPIN1. A series of cell functional experiments were performed to investigate whether the miR-381-mediated regulation of SPIN1 is involved in the progression and aggressiveness of CRC cells via the Wnt/β-catenin pathway. Our results showed that SPIN1 is frequently overexpressed in CRC tissues and cell lines, and its upregulation is positively correlated with disease progression and lymph node metastasis. Moreover, SPIN1 depletion suppresses cell growth, migration, and invasion through inactivation of the Wnt/β-catenin signaling pathway, which recapitulates the effects of miR-381 upregulation. Moreover, SPIN1 is a target gene of miR-381, and miR-381 is downregulated in CRC. Furthermore, the reintroduction of SPIN1 partially abolished the miR-381-mediated inhibitory effects in CRC cells. In summary, our data revealed that the miR-381/SPIN1 axis greatly contributes to CRC tumorigenesis by orchestrating the Wnt/β-catenin pathway, thereby representing actionable therapeutic targets for colorectal cancer patients.

WWP2 drives the progression of gastric cancer by facilitating the ubiquitination and degradation of LATS1 protein

“…Total RNA isolated from GC cells and xenograft tissues was extracted using TRIzol reagent (Invitrogen; Thermo Fisher Scientific, CA, USA) as previously described [ 26 ]. cDNA was obtained from total RNA using a reverse transcription kit (TransGen Biotech, Beijing, China).…”

miR‐3133 inhibits gastrointestinal cancer progression through activation of Hippo and p53 signalling pathways via multi‐targets

“…Total RNA was extracted from GC tissues, CRC tissues and paired adjacent noncancerous tissues. Further complementary DNA (cDNA) was obtained and Real‐time PCR was performed as previous described 29 . GAPDH served as an internal control.…”

“…Further complementary DNA (cDNA) was obtained and Real-time PCR was performed as previous described. 29 GAPDH served as an internal control. Relative mRNA expression of the indicated genes was calculated using the 2 −ΔΔCT method.…”

SPIN1 accelerates tumorigenesis and confers radioresistance of non-small cell lung cancer via orchestrating the FOXO3a/FOXM1 axis

“…The immunohistochemistry staining assay was performed according to the standard methods as we described previously (10,26). In brief, the para ned sections were depara nized and hydrated in sodium citrate buffer for antigen retrieval, and subsequently incubated with primary antibody against SPIN1 (1:100, 19531-1-AP, Proteintech) overnight at 4℃.…”

“…Several studies implied that SPIN1 could play a pivotal role in a plethora of physiological or pathological processes including skeletal muscle development regulation, cardiomyocyte proliferation evaluation, cell cycle progression and chromosomal stability maintenance (7)(8)(9). Subsequently, increasing evidence showed that human SPIN1 was frequently overexpressed in multiple malignant tumors, such as colorectal cancer, gastric cancer, glioma, and breast cancer (10)(11)(12)(13)(14), etc. For instance, SPIN1 triggers lipid metabolism and enhances cell growth of HCC cells via upregulation of FASN expression (11).…”