Open Access

Clinical significance and functional role of transmembrane protein 47 (TMEM47) in chemoresistance of hepatocellular carcinoma

  • Authors:
    • Kevin Tak‑Pan Ng
    • Oscar Wai‑Ho Yeung
    • Jiang Liu
    • Chang Xian Li
    • Hui Liu
    • Xiao Bing Liu
    • Xiang Qi
    • Yuen Yuen Ma
    • Yin Fan Lam
    • Matthew Yh Lau
    • Wen Qi Qiu
    • Hoi Chung Shiu
    • Man Kit Lai
    • Chung Mau Lo
    • Kwan Man
  • View Affiliations

  • Published online on: July 28, 2020     https://doi.org/10.3892/ijo.2020.5104
  • Copyright: © Ng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chemoresistance is the main cause of chemotherapy failure in patients with hepatocellular carcinoma (HCC). The gene encoding transmembrane protein 47 (TMEM47) was previously identified to be significantly upregulated in HCC cell lines with acquired chemoresistance. The aim of the present study was to characterize the clinical significance and function of TMEM47 in HCC chemoresistance. The results demonstrated that the TMEM47 expression levels in the tumors of patients not responding to cisplatin‑based transarterial chemoembolization (TACE) treatment was significantly higher compared with those in patients who responded to TACE treatment. Moreover, analyses from clinical samples and HCC cell lines indicated that TMEM47 expression may be upregulated in HCC in response to cisplatin treatment. Furthermore, the TMEM47 mRNA expression levels were positively correlated with the degree of cisplatin resistance of HCC cells. Overexpression of TMEM47 in HCC cells significantly promoted cisplatin resistance. The present study also demonstrated that targeted inhibition of TMEM47 could significantly reduce cisplatin resistance of cisplatin‑resistant HCC cells via enhancing caspase‑mediated apoptosis. In addition, targeted inhibition of TMEM47 enhanced the sensitivity of cisplatin‑resistant cells to cisplatin via suppressing cisplatin‑induced activation of the genes involved in drug efflux and metabolism. The present study also validated that TMEM47 expression was significantly correlated with multidrug resistance‑associated protein 1 in patients with HCC who received TACE treatment. In conclusion, the findings of the present study demonstrated that TMEM47 may be a useful biomarker for predicting the response to chemotherapy and a potential therapeutic target for overcoming HCC chemoresistance.

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Spandidos Publications style
Ng KT, Yeung OW, Liu J, Li CX, Liu H, Liu XB, Qi X, Ma YY, Lam YF, Lau MY, Lau MY, et al: Clinical significance and functional role of transmembrane protein 47 (TMEM47) in chemoresistance of hepatocellular carcinoma. Int J Oncol 0: 0-0, 1899
APA
Ng, K.T., Yeung, O.W., Liu, J., Li, C.X., Liu, H., Liu, X.B. ... Man, K. (1899). Clinical significance and functional role of transmembrane protein 47 (TMEM47) in chemoresistance of hepatocellular carcinoma. International Journal of Oncology, 0, 0-0. https://doi.org/10.3892/ijo.2020.5104
MLA
Ng, K. T., Yeung, O. W., Liu, J., Li, C. X., Liu, H., Liu, X. B., Qi, X., Ma, Y. Y., Lam, Y. F., Lau, M. Y., Qiu, W. Q., Shiu, H. C., Lai, M. K., Lo, C. M., Man, K."Clinical significance and functional role of transmembrane protein 47 (TMEM47) in chemoresistance of hepatocellular carcinoma". International Journal of Oncology 0.0 (1899): 0-0.
Chicago
Ng, K. T., Yeung, O. W., Liu, J., Li, C. X., Liu, H., Liu, X. B., Qi, X., Ma, Y. Y., Lam, Y. F., Lau, M. Y., Qiu, W. Q., Shiu, H. C., Lai, M. K., Lo, C. M., Man, K."Clinical significance and functional role of transmembrane protein 47 (TMEM47) in chemoresistance of hepatocellular carcinoma". International Journal of Oncology 0, no. 0 (1899): 0-0. https://doi.org/10.3892/ijo.2020.5104