About Us

We are one of the research laboratories within the Urothelial Carcinoma Research Team at Kaohsiung Medical University. Despite limited funding, experimental technology, and research manpower, we aim to contribute a small piece to the puzzle in the treatment blueprint for upper tract urothelial carcinoma (UTUC). We hope that, together with scholars worldwide researching UTUC, we can complete this blueprint and encourage each other in this shared endeavor.

 

Our laboratory mainly investigates the molecular mechanisms of UTUC. In Taiwan, the incidence ratio of bladder cancer to UTUC is 1.48:1, while in Western countries, it is 11.45:1. In the United States, renal cell carcinoma (RCC) is the predominant upper tract tumor, whereas in Taiwan, the incidence and prevalence of UTUC are notably high. Therefore, understanding whether unique environmental or genetic factors contribute to UTUC in Taiwan is a critical issue for the health of the local population.

 

Our laboratory has identified several potential independent prognostic markers for UTUC, including Osteopontin, COX-2, P53, Visfatin, HIF-1α, LEPR, STAT3, CSN6, TALDO1, CSF-1, ARF6, Derlin1, ATIC, and VEGFA. Additionally, we focus on investigating molecular mechanisms involving non-coding RNAs, particularly microRNAs (miRs) and long non-coding RNAs (LncRNAs).

 

MicroRNAs are short, non-coding RNA sequences, approximately 18 to 25 nucleotides in length, that regulate the expression of target genes by binding to the 5'-UTR, CDS, or 3'-UTR of the target gene's mRNA. To date, more than 4,000 microRNAs have been identified in human cells that regulate human gene expression. A single microRNA can regulate approximately 200 mRNAs, and each mRNA can be regulated by multiple microRNAs. Numerous studies have shown that microRNAs regulate various biological pathways, such as differentiation, proliferation, migration, and apoptosis. Additionally, microRNAs play critical roles in both oncogenic and tumor-suppressing mechanisms.

 

LncRNAs are long non-coding RNAs greater than 200 nucleotides in length. To date, more than 100,000 lncRNAs have been identified, and the number continues to increase. LncRNAs have been found to regulate cell proliferation, the cell cycle, metabolism, apoptosis, and differentiation. Furthermore, lncRNAs can regulate gene transcription, translation, and post-translational modifications, highlighting their critical role in biological processes. However, recent research has revealed that the abnormal expression of lncRNAs can promote tumor development and is associated with tumor invasion and metastasis. In addition to regulating gene expression, studies have shown that lncRNAs can act as competing endogenous RNAs (ceRNAs) by binding to microRNA response elements (MREs) of microRNAs, thereby preventing microRNAs from directly regulating the expression of downstream genes. To date, research on lncRNAs in upper tract urothelial carcinoma remains limited, making the impact of miRNAs, lncRNAs, and associated specific genes on UTUC worthy of further investigation.

 

Our laboratory has identified that the miR-145-5p/ARF6/MMP7, miR-145-5p/ATIC, miR-214-3p/CSF-1, miR-375-3p/Derlin1, and miR-299-3p/VEGFA pathways regulate the functions of UTUC cells. However, tumors are not caused by a single factor; they are induced through the dynamic interplay of multiple hallmark factors during tumor progression. In recent years, various hallmarks of tumors, including bladder cancer, have been gradually studied, but investigations into the hallmarks of UTUC remain limited.

 

Our ongoing research will further extend to deregulating cellular energetics (including glucose metabolism pathways, the non-oxidative pentose phosphate pathway, and the de novo purine biosynthetic pathway), resisting cell death (exploring resistance to first-line chemotherapy drugs such as cisplatin and gemcitabine, as well as autophagy), inducing metastasis, and evading immune destruction (investigating the roles of PD-L1, CSF-1, and IL-34 in the tumor microenvironment and immune suppression). We aim to integrate these studies into a comprehensive framework rather than isolated point-to-point approaches or linear pathways. Our ultimate goal is to discover effective treatments, and potentially preventive strategies, for UTUC.