Research Paper Volume 13, Issue 18 pp 22164—22175
SLCO1B3 promotes colorectal cancer tumorigenesis and metastasis through STAT3
- 1 Department of General Surgery, Hebei Medical University Third Affiliated Hospital, Shijiazhuang 050000, Hebei, China
- 2 Scientific Research Center, Hebei Medical University Fourth Affiliated Hospital, Shijiazhuang 050000, Hebei, China
- 3 The Second General Surgery, Hebei Medical University Fourth Affiliated Hospital, Shijiazhuang 050000, Hebei, China
- 4 The First General Surgery, The 980 Hospital of PLA Joint Service Support Force, Shijiazhuang 050000, Hebei, China
Received: February 18, 2021 Accepted: August 2, 2021 Published: September 15, 2021https://doi.org/10.18632/aging.203502
How to Cite
Copyright: © 2021 Zhi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
cDNA: complementary DNA; CRC: colorectal cancer; Ct-SLCO1B3: cancer-type SLCO1B3 mRNA; DEGs: differentially expressed genes; FBS: fetal bovine serum; GO: Gene Ontology; GSEA: Gene Set Enrichment Analysis; H&E: hematoxylin and eosin; KEGG: Kyoto Encyclopedia of Genes and Genomes; Lt-SLCO1B3: liver-type SLCO1B3 mRNA; OATP: organic anion-transporting polypeptide; OS: overall survival; qRT-PCR: quantitative real-time PCR.