SLCO1B3 promotes colorectal cancer tumorigenesis and metastasis through STAT3

Abstract

Solute carrier organic anion transporter family member 1B3 (SLCO1B3) is a gene that encodes an organic anion-transporting polypeptide (OATP) 1B3, a membrane-bound multi-specific transporter in hepatocytes. SLCO1B3 was first reported in hepatocytes. Later, it was found that its expression is higher in colorectal cancer (CRC) than in the adjacent normal tissue. However, the role of SLCO1B3 in CRC is not well elucidated. In this study, the correlation between SLCO1B3 and the overall survival (OS) of CRC patients was evaluated using data from the GEO database. This study evaluated the relationship between SLCO1B3 and the clinicopathological characteristics and prognosis of CRC patients. The effects of SLCO1B3 knockdown, on human CRC cell proliferation, migration, and invasion in vitro and CRC tumorigenesis and metastasis in vivo were also examined. In addition, next-generation sequencing was used to identify SLCO1B3 mediators. The results confirmed the association between SLCO1B3 and poor OS of CRC patients, and SLCO1B3 was identified as the top hub gene associated with the OS. The study showed that high SLCO1B3 expression was associated with poor tumor differentiation, advanced disease stage, tumor invasion, lymph node metastasis, and poor OS. Next-generation sequencing revealed that SLCO1B3 knockdown affected the expression of several genes involved in cancer invasion, metastasis, and DNA repair. Moreover, the western blot analysis showed that SLCO1B3 knockdown downregulated p-STAT3, MMP-2, and MMP-9. In summary, we demonstrated that SLCO1B3 acts as a novel carcinogen in the CRC that drives the CRC tumorigenesis and metastasis. SLCO1B3 inhibitors, alone or in combination with current drugs, may have therapeutic benefits in CRC.

CEBPB-mediated upregulation of SERPINA1 promotes colorectal cancer progression by enhancing STAT3 signaling

“…It was found that Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 to promote the growth of colorectal cancer cells [ 26 ]. SLCO1B3 can promote the proliferation and metastasis of colorectal cancer by activating the STAT3 pathway [ 27 ]. Previous studies have confirmed that the activation of STAT3 is related to the poor prognosis of tumors, including head and neck tumors, B-cell lymphoma, cervical cancer, gastric cancer, colon cancer, liver cancer, glioma and esophageal cancer [ 28 ].…”

Comprehensive analysis of scRNA-seq and bulk RNA-seq reveal the characteristics of disulfidptosis and a prognostic signature in BLCA

“…It transports several endogenous and exogenous compounds. SLCO1B3 contributes to the development of several cancers and regulates tumor sensitivity to chemotherapy [ 40 , 41 ]. Nonetheless, its expression and biological function in BLCA have never been reported.…”

A novel anoikis‐related prognostic signature associated with prognosis and immune infiltration landscape in lung adenocarcinoma

“…20 SLCO1B3 could be a novel carcinogen in colorectal cancer (CRC), which drives CRC tumor occur and metastasis. 21 In vivo tumor construction in non-small cell lung cancer cells is inhibited by cancer type-SLCO1B3 (Ct-SLCO1B3) knockdown. 22 As a tumor suppressor, CDX2 could inhibit Wnt/β-catenin signaling so that colon cancer cells cannot proliferate.…”

“…SLCO1B3 could be a novel carcinogen in colorectal cancer (CRC), which drives CRC tumor occur and metastasis 21 . In vivo tumor construction in non‐small cell lung cancer cells is inhibited by cancer type‐SLCO1B3 (Ct‐SLCO1B3) knockdown 22 …”