TREM2 promotes the proliferation and invasion of renal cell carcinoma cells by inhibiting the P53 signaling pathway

Abstract

Renal cell carcinoma (RCC) is a prevalent malignancy characterized by poor prognosis and high mortality. The role of triggering receptor expressed on myeloid cells-2 (TREM2) in RCC progression has been increasingly recognized, yet its underlying mechanisms remain to be fully elucidated. The aim of the present study was to assess the effects of TREM2 on RCC cells and its potential mechanisms. Lentiviral transfection was used to knockdown and overexpress TREM2 in RCC cells, and the expression level of TREM2 was evaluated using reverse transcription-quantitative PCR. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to assess the proliferation of the RCC cells. Cell migration and invasion was evaluated using the wound healing assay and Transwell assay, respectively. Western blotting was used to assess the expression levels of TREM2, P53, p-P53, P21 and p-P21 in TREM2 knockdown or overexpression RCC cells. The results demonstrated that the expression level of TREM2 was significantly higher in cancer tissues compared with adjacent normal tissues. The results of the CCK-8 and EdU assays demonstrated that knockdown of TREM2 significantly inhibited the proliferation of RCC cells, whilst overexpression of TREM2 enhanced the proliferation of RCC cells. The results of the wound healing and Transwell assay revealed that, compared with the control group, the overexpression of TREM2 significantly increased the migration and invasion of RCC cells, whereas knockdown of TREM2 significantly decreased the migration of RCC cells. In addition, western blotting demonstrated that the phosphorylation levels of P53 and P21 proteins were significantly increased after TREM2 knockdown in RCC cells. In conclusion, TREM2 is highly expressed in RCC tissues and promotes the migration of RCC cells by inhibiting the P53 signaling pathway. The present study provides new insights into the regulatory effect of TREM2 on RCC and further reveals the potential of TREM2 as a therapeutic target for RCC.

Keywords: P53; migration; proliferation; renal cell carcinoma; triggering receptor expressed on myeloid cells-2.

Figure 1.

High expression of TREM2 in RCC tissues. Reverse transcription-quantitative PCR was used to detect the expression of TREM2 in (A) 10 cases of RCC and matched adjacent normal tissues and (B) HK-2 and ACHN cells. **P<0.01, ****P<0.0001. TREM2, triggering receptor expressed on myeloid cells-2.

Figure 2.

TREM2 promotes the proliferation of RCC cells. ACHN cells were infected with the corresponding lentiviruses (sh-NC, sh-TREM2, vector and TREM2). After 48 h, cells were collected and the results of the knock-down and overexpression of TREM2 was assessed using (A) reverse transcription-quantitative PCR and (B) western blotting. (C) Cell Counting Kit-8 and (D) EdU assays were used to detect the effect of the knockdown or overexpression of TREM2 on the viability and proliferation of RCC cells. **P<0.01. TREM2, triggering receptor expressed on myeloid cells-2; RCC, renal cell carcinoma; sh, short hairpin; NC, negative control; EdU, 5-ethynyl-2′-deoxyuridine.

Figure 3.

TREM2 promotes migration of RCC cells. (A) Wound healing assay and (B) Transwell assays were used to assess the effect of the knockdown or overexpression of TREM2 on the migration and invasion of RCC cells. (A) Magnification, ×100. (B) Scale bar, 50 µm. **P<0.01. TREM2, triggering receptor expressed on myeloid cells-2; RCC, renal cell carcinoma; sh, short hairpin; NC, negative control.

Figure 4.

TREM2 promotes the proliferation of renal cell carcinoma cells by inhibiting the P53 signaling pathway. (A) Western blotting was used to assess the effects of the knockdown or overexpression of TREM2 on the protein and phosphorylation levels of P53 and P21, as well as the phosphorylation levels. (B) Semi-quantitative results of P53, p-P53, P21 and p-P21 protein bands. Relative ratio of (C) p-P53/P53 and (D) p-P21/P21. **P<0.01. TREM2, triggering receptor that is expressed on myeloid cells-2; sh, short hairpin; NC, negative control.