Increasing evidence indicates that long noncoding RNA SPRY4 intronic transcript 1 (lncRNA
SPRY4-IT1
) has been reported to be associated with the progression of several cancers, but its expression level and the function of SPRY4-IT1 in the progression of gastric cancer (GC) have been rarely reported. Here we found that SPRY4-IT1 was upregulated in GC.
In vitro
experiments revealed that SPRY4-IT1 knockdown significantly inhibited GC cell proliferation by causing G1 arrest and promoting apoptosis, whereas SPRY4-IT1 overexpression promoted cell growth. Further functional assays indicated that SPRY4-IT1 overexpression significantly promoted cell migration and invasion. Bioinformatics analysis predicted that there is a SPRY4-IT1/miR-101-3p/AMPK axis in GC progression. A dual-luciferase reporter system validated the direct interaction of SPRY4-IT1, miR-101-3p, and AMPK. Western blot verified that the inhibition of SPRY4-IT1 decreased AMPK expression. Furthermore, silencing SPRY4-IT1 suppressed GC growth
in vivo
. Importantly, we demonstrated that SPRY4-IT1 was upregulated in serum exosomes from GC patients and correlated with cancer metastasis. Altogether, silencing SPRY4-IT1 suppresses the progression of GC by interacting with miR-101-3p and decreasing inhibiting AMPK expression. Taken together, our study demonstrates that SPRY4-IT1 could act as a potential therapeutic target for GC patients.
Resistance to chemotherapy is a big challenge for treatment of patients with colorectal cancer; however; the mechanism underlying chemoresistance in colorectal cancer cell has not been elucidated. MicroRNAs (miRNAs) are new players in the development of drug chemoresistance. In our study, we indicated that overexpression of miR-761 promoted the sensitivity of colorectal cancer cells to 5-Fluorouracil (5-FU). miR-761 expression was downregulated in colorectal cancer cell lines and tissues. miR-761 expression was lower in patients with low grade than in patients with high grade. In additon, we showed that elevated expression of miR-761 suppressed colorectal cancer cell proliferation, cell cycle, colony formation and cell invasion. We identified that FOXM1 was a direct target gene of miR-761 in colorectal cancer cell. FOXM1 expression was upregulated in colorectal cancer tissues compare to the adjacent non-tumor tissues. MiR-761 expression was negatively associated with the expression of FOXM1 in colorectal cancer tissues. Elevated expression of FOXM1 suppressed the sensitivity of miR-761-overexpressing HT29 cells to 5-FU. We also indicated that FOXM1 overexpression promoted cell proliferation, cycle and invasion of miR-761-overexpressing HT29 cells. These data suggested that miR-761 played a tumor suppressor miRNA in colorectal cancer progression and reduced miR-761 expression might be a major mechanism for 5-FU resistance in colorectal cancer cell.
Our study demonstrated that high expression of c-erbB-2 protein was strongly associated with lymph node metastasis, histological differentiation and 5-year survival rate in GC patients after surgery.
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