As TRIM65 has an RBCC (RING, B‐box and coiled‐coil) ubiquitin ligase domain,[22] the first and second Cystine (Cys12 and Cys15) in the TRIM65 RING domain were mutated to Alanine or Serine (TRIM65‐CAmut and TRIM65‐CSmut, respectively) to destroy the E3 ligase activity[30] and the two mutants were co‐transfected with siTRIM65 to HCC cells (Figure 3A). The gene discussed is TRIM65; the disease is hepatocellular carcinoma.