CircTNPO3 promotes hepatocellular carcinoma progression by sponging miR‐199b‐5p and regulating STRN expression

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver tumor, which seriously threatens human health. CircTNPO3 was up‐regulated in HCC tissues. However, the regulatory mechanism of circTNPO3 in HCC was still unclear. We aimed to investigate the circTNPO3 function in the development of HCC. qRT‐PCR and Western blot examined gene and protein levels. CCK8, EdU, flow cytometry, and Transwell assays were used to detect cell viability, proliferation, apoptosis, and invasion abilities. Dual‐luciferase reporter and RIP assays determined the relationship between circTNPO3, miR‐199b‐5p, and striatin (STRN). The effect of CircTNPO3 on HCC progress was investigated in vivo. CircTNPO3 and STRN were significantly increased, while miR‐199b‐5p was repressed in HCC tissues or cells. Afterward, miR‐199b‐5p was negatively correlated with STRN. circTNPO3 was positively correlated with STRN. Knockdown of circTNPO3 inhibited cell viability, proliferation, invasion, and promoted apoptosis, while circTNPO3 overexpression had the opposite results. Furthermore, miR‐199b‐5p inhibition could eliminate the regulatory effect of sh‐circTNPO3 on the proliferation and apoptosis in HCC cells. CircTNPO3 positively regulated STRN expression by targeting miR‐199b‐5p. MiR‐199b‐5p suppressed HCC progression by inhibiting STRN expression. Tumor formation in nude mice showed that knockdown of circTNPO3 significantly inhibited tumor growth and suppressed ki‐67 levels. CircTNPO3 promoted HCC progression through regulating STRN expression by sponging miR‐199b‐5p, which provided a strategy for HCC treatment.

Cellular Impacts of Striatins and the STRIPAK Complex and Their Roles in the Development and Metastasis in Clinical Cancers (Review)

“…Furthermore, the interaction between YSK1 and STRN1 was shown to facilitate EMT in HCC, regulating energy reserves through modifying cancer cells’ lipid metabolism [ 114 ]. The role of miRNA in cancer is also emerging, with STRN1 found to be a downstream target of miRNAs such as miR-199B-5P, which inhibits HCC progression by limiting the expression of STRN1 [ 130 ].…”

The role of circRNAs in regulation of drug resistance in ovarian cancer

“…CircTNPO3 suppressed tumor metastasis via interaction with IGF2BP3 and destabilization of SERPINH1 mRNA in clear cell renal cell carcinoma ( Pan et al, 2022b ). CircTNPO3 enhanced tumor progression via upregulation of STRN expression by decoying miR-199b-5p in hepatocellular carcinoma ( Liu and Liu, 2023 ). CircTNPO3 expression was increased in ovarian cancer tissues and associated with PTX resistance.…”