Targetting an LncRNA P5848-ENO1 axis inhibits tumor growth in hepatocellular carcinoma.

Xidan Zhu,Guangrong Li,Baolin Li,Zhangrui Zeng,Jing Quan,Hui Yu,Jinbo Liu

doi:10.1042/bsr20180896

Xidan Zhu, Guangrong Li + Show 5 more

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https://doi.org/10.1042/bsr20180896

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Abstract

Hepatocellular carcinoma (HCC) has a high recurrence rate and poor clinical outcome after currently used therapies, including radiofrequency ablation. To explore the possible mechanisms for the relapse of HCC, in the present study we focussed on long non-coding RNA (LncRNA), which has been reported to be involved in tumorigenesis. We identified an LncRNA P5848, whose expression level was up-regulated in tumor samples from HCC patients after radiofrequency ablation. As such, we speculated that LncRNA P5848 may play a role in tumor growth. Here we showed that LncRNA P5848, whose up-regulation can lead to HCC cancer cell proliferation and migration. In vitro and in vivo overexpression of LncRNA P5848 promoted cell growth, cell survival, and cell invasion, whereas LncRNA P5848 depletion exerts opposite effects. Mechanistically, we have found that ENO1 was the target of LncRNA P5848. LncRNA P5848 up-regulated the gene and protein expression level of ENO1, promoting tumor growth and cell survival. However, siRNA-mediated knockdown of ENO1 counteracted the effects of LncRNA P5848 on cancer cell growth, cell survival, and migration. Taken together, LncRNA P5848 promotes HCC development by up-regulating ENO1, indicating that LncRNA P5848-ENO1 axis is a potential therapeutic target for the treatment of HCC.

Highlights

Hepatocellular carcinoma (HCC) is a common and deadly cancer, constituting the second most common cause of cancer deaths in developing nations and the sixth most common cause in developed countries [1]
Since there are compelling evidence showing that long non-coding RNA (LncRNA) have been implicated in tumor onset, progression, and metastasis, in the present study we focussed on the role of LncRNA in HCC
To start the study on the role of LncRNA P5848 in HCC, we first noticed the relapse of HCC after radiofrequency ablation in patients in the clinic and we found that the expression of LncRNA P5848 was increased after heat and radiofrequency ablation via Chip data (Figure 1A,B)

Summary

Introduction

Hepatocellular carcinoma (HCC) is a common and deadly cancer, constituting the second most common cause of cancer deaths in developing nations and the sixth most common cause in developed countries [1]. Despite considerable efforts and advances aimed at understanding HCC-related tumorigenesis, metastasis, and treatment, morbidity and mortality continue to rise [2]. Radiofrequency ablation is a currently used therapeutic strategy for the treatment of HCC in the clinic, the relapse often occurs, which acquires the mechanistic exploration. Accumulating evidence suggests that long non-coding RNA (LncRNA) has been implicated in the tumorigenesis via regulating cancer cell proliferation, cell survival, and migration/metastases [3,4]. The tumor hyperthermia has been listed as the sixth anticancer strategy after surgery, radiotherapy, chemotherapy, targetted therapy, and immunotherapy. It has many advantages, being non-invasive, painless, safe and reliable and easy to operate. Our previous experiment showed that LncRNA P5848 was up-regulated after heat exposure and combined with hyperthermia for tumor killing

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