[Preliminary Study of the Role of INPP4B in Promoting Colorectal Cancer Metastasis and the Mechanisms Involved].

OBJECTIVE

To investigate the expression of inositol polyphosphate 4-phosphatase type Ⅱ B (INPP4B) in colorectal cancer (CRC) and the relevant clinical significance, to determine the relationship between INPP4B and matrix metallopeptidase 7 (MMP7) in CRC cells, and to make preliminary exploration of the effects of INPP4B on the proliferation and migration of CRC cells and mechanisms involved.

METHODS

The TIMER2.0 and GEPIA2 databases were used to analyze the differences in expression between cancer and para-cancerous tissues and the effects of such differences on the prognosis of CRC. The expression of INPP4B in 102 surgically resected CRC tumors was determined by immunohistochemistry (IHC), and the correlation between INPP4B and clinical pathological indicators was analyzed. In CRC cells with overexpressed/knocked-down , the expression of and were examined by real time fluorogenic quantitative PCR, the protein expression of INPP4B was assessed by Western blot, cell proliferation was determined using the CellTiter 96® AQueous One assay, and cell migration and invasion were assessed using wound healing assay and real-time label-free dynamic cell analysis (RTCA). The LinkedOmics database was used to analyze signaling pathways related to function, and the role of potential key molecules was validated at the cellular level.

RESULTS

Analysis with the TIMER2.0 database and GEPIA2 database showed elevated expression (colon adenocarcinoma [COAD]: 2.30, rectal adenocarcinoma [READ]: 2.33) in CRC compared to normal tissue (COAD: 1.91, READ: 1.89). IHC testing confirmed that INPP4B was upregulated in clinical CRC tissues and paracancerous tissues (<0.001). Cox regression model analysis showed that (hazards ratio [HR]=1.457, 95% confidence interval [CI]: 1.003-2.115) affected the prognosis of CRC, and the Kaplan-Meier curve showed that patients with high expression had shorter overall survival (<0.05). test was performed to analyze the relationship between INPP4B expression and clinicopathological indexes, and it was found that high expression of INPP4B was correlated with lymph node metastasis ( =3.997, =0.046) and neural invasion( =8.511, =0.004). In experiments, CRC cells overexpressing showed a significantly increased cell proliferation and migration compared to the cells in the control group (<0.05). Analysis using the LinkedOmics database showed that was correlated with extracellular matrix remodeling and cell migration. Pearson's correlation analysis showed that MMP7 was positively correlated with INPP4B (=0.3782, <0.001). overexpression or knockdown also led to the upregulation or the downregulation of expression in CRC cells.

CONCLUSION

INPP4B is highly expressed in CRC tissues and significantly correlated with lymph node metastasis, neural invasion, and patient prognosis. may mediate the role of INPP4B in promoting CRC cell migration and invasion.