Depletion of the triggering receptor expressed on myeloid cells 2 inhibits progression of renal cell carcinoma via regulating related protein expression and PTEN-PI3K/Akt pathway

Abstract

The triggering receptor expressed on myeloid cells 2 (TREM-2) is suggested to be involved in the development of certain human malignancies. However, the functions of TREM-2 in renal cell carcinoma (RCC) are still less known. To reveal the effects of TREM-2 on the RCC progression, we examined the TREM-2 expression in RCC tumor tissues. Then, we analyzed the cell proliferation, cell apoptosis, cell cycle and expression of the relative factors in two selected RCC cell lines post RNA interference. We also analyzed the functions of TREM-2 in an in vivo nude mouse model. We found that, the expression of TREM-2 was abnormally elevated in RCC tumor tissues. Silencing TREM-2 inhibited cell growth, induced G1 phase arrest of cell cycle and cell apoptosis in RCC cells. In vivo, the results showed that depletion of TREM-2 significantly inhibited the ACHN tumor growth in the nude mouse model. The analysis of relative protein factors suggested that silencing TREM-2 downregulated the expression levels of Bcl2 and PCNA, and upregulated the expression levels of Bax and caspase-3 in RCC cell lines. Depletion of TREM-2 inactivated PI3K/Akt pathway through increasing the expression of PTEN. Taken together, TREM-2 acts as an oncogene in the development of RCC and can be considered as a novel therapeutic factor in the treatment of RCC.

TRIP13 promotes metastasis of colorectal cancer regardless of p53 and microsatellite instability status

“…Our RNA sequencing studies with TRIP13 knockdown cells identified downstream molecular targets, including COL6A3 (collagen/extracellular matrix), TREM2 (inflammation), SHC3 (MVP/MEK/ERK activation), and KLK7 (MAPK signaling). Prior studies have implicated these TRIP13 targets in the progression of various cancers, including COL6A3 [44,45] and KLK7 [46] in CRCs, SHC3 in hepatocellular carcinomas [47], and TREM2 in gastric cancers [48] and renal cell carcinomas [49]. Our findings were validated with human samples, which showed upregulation of COL6A3, KLK7, TREM2, and SHC3 in CRCs compared to matched normal colon tissues.…”

“…Genes modulated by TRIP13 knockdown included COL6A3, KLK7, TREM2, and SHC3. COL6A3 [44,45] and KLK7 [46] in CRCs, SHC3 in hepatocellular carcinomas [47], and TREM2 in gastric cancers [48] and renal cell carcinomas [49] are associated with tumor growth. We showed decreased mRNA expression of COL6A3, KLK7, TREM2, and SHC3 after TRIP13 knockdown in CRC cells (Fig.…”

TREM-1 and TREM-2 Expression on Blood Monocytes Could Help Predict Survival in High-Grade Glioma Patients

“…Zhang et al showed high TREM-2 expression in renal cell carcinoma. Knockdown of TREM-2 inhibited cell growth and induced cell cycle arrest and apoptosis of tumor cells [ 48 ]. On the contrary, in a recent study from 2019, Tang et al described TREM-2 as a tumor suppressor.…”

Function of TREM1 and TREM2 in Liver-Related Diseases

“…Aside from HCC, TREM2 has also been studied in many other tumors, such as colorectal carcinoma, lung cancer, and glioma [124][125][126][127][128]. However, it remains to be explored whether the mechanism of TREM2 in liver tumors and other tumors is consistent.…”