HHLA2 and nonpapillary renal cell carcinoma: As shown in Fig. 4a–c, the knockdown expression of HHLA2 significantly increased the ratio of G1 phase and induced cell cycle arrest in human ccRCC cell lines, we then further examined the expressions of Cyclin D1, c-Myc and Cyclin E1 at the protein level in knockdown group cells in contrast to the control group cells.