Targeted Silencing of Kim-1 Inhibits the Growth of Clear Cell Renal Cell Carcinoma Cell Line 786-0 In Vitro and In Vivo

Yotis

et al. 2021

Sci Rep

Metastasis is present in approximately 30% of patients diagnosed with renal cell carcinoma (RCC) and is associated with a 5-year survival rate of < 15%. Kidney injury molecule 1 (KIM-1), encoded by the HAVCR1 gene, is a proximal tubule cell-surface glycoprotein and a biomarker for early detection of RCC, but its pathophysiological significance in RCC remains unclear. We generated human and murine RCC cell lines either expressing or lacking KIM-1, respectively, and compared their growth and metastatic properties using validated methods. Surprisingly, KIM-1 expression had no effect on cell proliferation or subcutaneous tumour growth in immune deficient (Rag1−/−) Balb/c mice, but inhibited cell invasion and formation of lung metastasis in the same model. Further, we show that the inhibitory effect of KIM-1 on metastases was observed in both immune deficient and immune competent mice. Transcriptomic profiling identified the mRNA for the pro-metastatic GTPase, Rab27b, to be downregulated significantly in KIM-1 expressing human and murine RCC cells. Finally, analysis of The Cancer Genome Atlas (TCGA) data revealed that elevated HAVCR1 mRNA expression in the two most common types of RCC, clear cell and papillary RCC, tumours correlated with significantly improved overall patient survival. Our findings reveal a novel role for KIM-1 in inhibiting metastasis of RCC and suggests that tumour-associated KIM-1 expression may be a favourable prognostic factor.

Section: Introductioncontrasting

confidence: 99%

Kidney injury molecule-1 inhibits metastasis of renal cell carcinoma

Yotis

et al. 2021

Sci Rep

“…However, it seems that normal saline with mannitol is inferior to saline alone or in combination with furosemide in cisplatin associated acute renal failure. Despite not being able to influence cisplatin cellular accumulation, normal saline alters cellular sensitivity to the chemotherapeutic agent [152]. Magnesium has also proven to be effective in combination with proper hydrating regimens [153].…”

Section: Strategies To Prevent Cisplatin Nephrotoxicitymentioning

confidence: 99%

The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity

Tănase

Gosav

Radu

et al. 2019

IJMS

125

Acute kidney injury (AKI) following platinum-based chemotherapeutics is a frequently reported serious side-effect. However, there are no approved biomarkers that can properly identify proximal tubular injury while routine assessments such as serum creatinine lack sensitivity. Kidney-injury-molecule 1 (KIM-1) is showing promise in identifying cisplatin-induced renal injury both in vitro and in vivo studies. In this review, we focus on describing the mechanisms of renal tubular cells cisplatin-induced apoptosis, the associated inflammatory response and oxidative stress and the role of KIM-1 as a possible biomarker used to predict cisplatin associated AKI.

“…HAVCR1 is significantly upregulated in human colorectal cancer [ 34 ]. Targeted silencing of HAVCR1 inhibits clear cell renal cell carcinoma cells growth in vitro and in vivo [ 35 ]. In addition, HAVCR1 has been found to modulate the MEK/ERK pathway in GAC and influence tumor progression and patient outcomes [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA AL139002.1 promotes gastric cancer development by sponging microRNA-490-3p to regulate Hepatitis A Virus Cellular Receptor 1 expression

Chen

Zhang

2021

Bioengineered

Mounting evidence suggests that lncRNA regulates many important diseases. However, the biological role of most lncRNAs in gastric cancer (GC) remain unclear. In this paper, we determined differential expression of lncRNAs and predicted ceRNA networks in the GC database by bioinformatics analysis and validated in GC cells. The effect of lncRNA AL139002.1 on GC cells biological function was assessed by flow cytometry, CCK-8, colony formation, wound healing assay, transwell, western blot, and qRT-PCR. And the relationship of lncRNA AL139002.1 or HAVCR1 with miR-490-3p was verified by luciferase reporter assay. The results showed that lncRNA AL139002.1 was highly expressed in GC cells and lncRNA AL139002.1 knockdown induced apoptosis, while suppressed cell proliferation, migration, invasion, and EMT. Functional examining indicated that lncRNA AL139002.1 regulated HAVCR1 expression by competitively binding miR-490-3p. In addition, lncRNA AL139002.1/miR-490-3p/HAVCR1 regulated EMT and metastasis through MEK/ERK signaling. In conclusion, lncRNA AL139002.1 was highly expressed in GC cells, and lncRNA AL139002.1/miR-490-3p/HAVCR1 functioned critically in GC by regulating MEK/ERK signaling. Our findings demonstrated that lncRNA AL139002.1 served as a potential therapeutic and antimetastatic biotarget for GC.