Downregulation of circular RNA circPVT1 restricts cell growth of hepatocellular carcinoma through downregulation of Sirtuin 7 via microRNA‐3666

Abstract

Circular RNAs (circRNAs) have been identified recently as pivotal regulators in the development and progression of cancers, generally by acting as competing endogenous RNAs of microRNAs (miRNAs) to regulate gene expression. The dysregulation of circRNAs in hepatocellular carcinoma (HCC) has attracted much attention, but the precise role of circRNAs in HCC remains largely unknown. In this study, we aimed to investigate the potential role of circular RNA PVT1 (circPVT1), a newly identified cancer‐related circRNA, in HCC. Herein, we found that circPVT1 expression was significantly upregulated in HCC tissues and cell lines. Knockdown of circPVT1 significantly reduced the growth and colony formation, and increased cell apoptosis, of HCC cells. Our results further identified circPVT1 as a sponge for miR‐3666. Knockdown of circPVT1 significantly increased miR‐3666 expression in HCC cells. Moreover, miR‐3666 expression was significantly downregulated in HCC tissues and was inversely correlated with circPVT1 expression. In addition, the overexpression of miR‐3666 inhibited the growth of HCC cells by targeting Sirtuin 7 (SIRT7). Notably, miR‐3666 inhibition or SIRT7 overexpression partially reversed the circPVT1 knockdown‐mediated inhibitory effect on HCC cell growth. Overall, these results demonstrate that downregulation of circPVT1 represses HCC cell growth by upregulating miR‐3666 to inhibit SIRT7, suggesting circPVT1 as a potential therapeutic target for HCC. Our study highlights the involvement of circPVT1/miR‐3666/SIRT7 in regulating HCC cell growth.

<p>CircPVT1 Regulates Cell Proliferation, Apoptosis and Glycolysis in Hepatocellular Carcinoma via miR-377/TRIM23 Axis</p>

“…22 CircPVT1 was reported to be upregulated and could promote HCC cell proliferation by targeting miR-3666 and regulating Sirtuin 7 expression. 23 Consistent with previous reports, we found that circPVT1 level was elevated in HCC tissues and cells, and circPVT1 silence hampered HCC progression in vitro and in vivo. All these results suggested that circPVT1 played an oncogenic role in HCC.…”

CircIL4R facilitates the tumorigenesis and inhibits ferroptosis in hepatocellular carcinoma by regulating the miR‐541‐3p/GPX4 axis

“…Similarly, hsa_circRNA_100084/ miR-23a-5p/IGF2 (J. Yang et al, 2020) and circPVT1/miR-3666/ SIRT7 (Li et al, 2020) axes were also discovered in researching HCC progression. There were reasons to believe that the miR-541-3p/ GPX4 axis was accountable for the regulatory role of circIL4R in oncobiology and ferroptosis in HCC.…”

“…For instance, hsa_circRNA_00278 regulated breast cancer cellular processes via miR‐328‐3p/COL1A1 axis (Liu, Ye, Ye, Lu, & Han, 2020); hsa_circRNA_0000069 facilitated cervical cancer proliferation and metastasis via miR‐873‐5p/TUSC3 axis (Zhang, Chen, Sun, An, & Xi, 2020); and circNTRK2 served as a tumorigenic role in esophageal squamous cell carcinoma by sponging miR‐140‐3p to up‐regulate NRIP1 (Chen et al, 2020). Similarly, hsa_circRNA_100084/miR‐23a‐5p/IGF2 (J. Yang et al, 2020) and circPVT1/miR‐3666/SIRT7 (Li et al, 2020) axes were also discovered in researching HCC progression. There were reasons to believe that the miR‐541‐3p/GPX4 axis was accountable for the regulatory role of circIL4R in oncobiology and ferroptosis in HCC.…”

Prognostic and clinicopathological value of circPVT1 in human cancers: A meta‐analysis

“… 23 , 32 By downregulating Sirtuin7(SIRT7) via sponging miR‐3666, circPVT1 can promote tumor growth and inhibit cell apoptosis in HCC. 33 Numerous studies have highlighted that circPVT1 can enhance cancer drug resistance and contribute to worse clinical outcome of cancer patients, indicating that targeting circPVT1 may be a promising therapeutic strategy to overcome chemoresistance and improve prognosis of cancer patients. For example, exosomal circPVT1 has been found to induce cisplatin resistance by stimulating YAP1 via sponging miR‐30a‐5p in GC in both vivo and vitro.…”