TPM4 aggravates the malignant progression of hepatocellular carcinoma through negatively regulating SUSD2.

OBJECTIVE

The aim of this study was to elucidate the role of TPM4 in the progression of hepatocellular carcinoma (HCC), and to explore the potential underlying mechanism by interacting with SUSD2.

PATIENTS AND METHODS

TPM4 expression levels in 41 HCC tissues and paracancerous tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between TPM4 level with the pathological indexes and overall survival of HCC patients was analyzed. TPM4 overexpression and knockdown models were constructed in Bel-7402 and Hep3B cells, respectively. Subsequently, Cell Counting Kit-8 (CCK-8) and transwell assay were conducted to assess the effects of TPM4 on the proliferative and migratory abilities of HCC cells. Dual-Luciferase reporter gene assay was performed to verify the binding relationship between TPM4 and SUSD2. In addition, the xenograft model was conducted in HCC-bearing mice administrated with Hep3B cells in vivo. Finally, the effect of TPM4 on the growth of HCC was explored.

RESULTS

TPM4 was significantly upregulated in HCC tissues and cell lines. Higher rates of lymphatic and distant metastasis, as well as worse prognosis, were observed in HCC patients with higher expression level of TPM4. The overexpression of TPM4 significantly enhanced the viability and migration abilities of Bel-7402 cells. However, opposite results were observed after the knockdown of TPM4 in Hep3B cells. SUSD2 was verified to be the target of TPM4 and was negatively regulated by TPM4. SUSD2 was lowly expressed in HCC tissues and cell lines. Meanwhile, SUSD2 was considered to be responsible for TPM4-regulated progression of HCC. In mice administrated with Hep3B, the cells transfected with sh-TPM4, the tumor volume and weight of HCC were markedly reduced when compared with the controls.

CONCLUSIONS

TPM4 level is correlated with high rates of lymphatic and distant metastasis, as well as poor prognosis of HCC patients. By negatively targeting SUSD2, TPM4 aggravates the progression of HCC by accelerating the proliferative and migratory abilities of HCC cells.