MicroRNA-197 promotes proliferation and inhibits apoptosis of gallbladder cancer cells by targeting insulin-like growth factor-binding protein 3

MicroRNA-197通过靶向胰岛素样生长因子结合蛋白3促进胆囊癌细胞增殖并抑制其凋亡

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作者:Li Tong, Jinglin Cheng, Heping Zuo, Jingrong Li

Background

Gallbladder cancer (GBC) is one of the common malignant tumors of the biliary tract. There is no report that miR-197 is involved in GBC. Objectives: The relationship between miR-197 expression and survival time of GBC patients was analyzed. Furthermore, the role and mechanism of miR-197 in GBC was explored. Material and

Conclusions

Our study proved that the expression of miR-197 is closely related to the poor prognosis of GBC. The miR-197-IGFBP3 axis regulates the proliferation and apoptosis of GBC cells. Downregulation of miR-197 inhibited the proliferation and promoted the apoptosis of GBC cells, indicating potential therapeutic effects.

Material and methods

A total of 39 GBC patients (21 males, 18 females; average age 56.1 ±8.5 years) were included from December 2013 to November 2014. All patients were admitted to our hospital for surgical treatment (excluding patients with preoperative chemotherapy). The expression of miR-197 in GBC tissues was examined, and the relationship between miR-197 and patient survival time was analyzed. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect cell proliferation. Flow cytometry and TUNEL staining were used to detect apoptosis. Expressions of proteins related with proliferation and apoptosis were detected. The target of miR-197 was predicted through bioinformatics website and verified using the dual luciferase reporter gene assay. The target gene was interfered to so that the effect of miR-197 on the regulation of GBC cell proliferation and apoptosis could be observed.

Methods

A total of 39 GBC patients (21 males, 18 females; average age 56.1 ±8.5 years) were included from December 2013 to November 2014. All patients were admitted to our hospital for surgical treatment (excluding patients with preoperative chemotherapy). The expression of miR-197 in GBC tissues was examined, and the relationship between miR-197 and patient survival time was analyzed. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect cell proliferation. Flow cytometry and TUNEL staining were used to detect apoptosis. Expressions of proteins related with proliferation and apoptosis were detected. The target of miR-197 was predicted through bioinformatics website and verified using the dual luciferase reporter gene assay. The target gene was interfered to so that the effect of miR-197 on the regulation of GBC cell proliferation and apoptosis could be observed.

Results

MiR-197 was highly expressed in GBC tissues, and the expression was closely related to the poor prognosis of GBC. Downregulation of miR-197 inhibited the proliferation and promoted the apoptosis of GBC cells; it also decreased the expressions of proliferation-related proteins p-ERK1/2 and p-AKT, and increased that of apoptosis pathway-related proteins Bax/Bcl-2 and c-caspase-3. The upregulation of miR-197 induced an opposite trend. MiR-197 directly regulated IGFBP3. Conclusions: Our study proved that the expression of miR-197 is closely related to the poor prognosis of GBC. The miR-197-IGFBP3 axis regulates the proliferation and apoptosis of GBC cells. Downregulation of miR-197 inhibited the proliferation and promoted the apoptosis of GBC cells, indicating potential therapeutic effects.

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