Overexpression of miR‐623 suppresses progression of hepatocellular carcinoma via regulating the PI3K/Akt signaling pathway by targeting XRCC5

Abstract

It has been reported that miR‐623 is deregulated in lung adenocarcinoma and inhibits tumor growth and invasion. However, it is unclear whether miR‐623 has a role in the progression of hepatocellular carcinoma (HCC). Herein, we found that miR‐623 was significantly downregulated in HCC, and that its expression was related to poor clinical outcomes of patients with HCC. Upregulation of miR‐623 decreased cell proliferation, viability, migration, and invasion and further promoted apoptosis in 7721, Huh7, and Bel‐7402 cells. Moreover, we also observed that miR‐623 regulated the phosphoinositide 3‐kinase/protein kinase B (PI3K/Akt), Wnt/β‐catenin, and extracellular regulated protein kinases/c‐Jun N‐terminal kinase (ERK/JNK) signaling pathways as well as the expression level of related proteins. Further, X‐ray repair cross complementing 5 (XRCC5) was a direct target for miR‐623, and the suppression of PI3K/Akt, Wnt/β‐catenin, and ERK/JNK signaling pathways and cell proliferation and invasion abilities caused by miR‐623 in HCC cells was significantly reversed by the upregulation of XRCC5. Collectively, our data suggested that miR‐623 suppressed the progression of HCC by regulating the PI3K/Akt, Wnt/β‐catenin, and ERK/JNK pathways by targeting XRCC5 in HCC in vitro, indicating that miR‐623 may be a target for the therapy of HCC.

Circ_0000144 functions as a miR-623 sponge to enhance gastric cancer progression via up-regulating GPRC5A

“…manifested that miR-623 inhibited pancreatic cancer metastasis in vitro and in vivo through targeting matrix metalloproteinase-1 (MMP1) [ 16 ]. Ren and colleagues illuminated that miR-623 functioned as a tumor suppressor in hepatocellular carcinoma through modulating the phosphoinositide 3‐kinase/protein kinase B (PI3K/Akt) pathway via targeting X-ray repair cross complementing 5 (XRCC5) [ 27 ]. In the current study, our data demonstrated that low miR-623 level was associated with a poor clinical outcome of GC patients.…”

CircRNA ZNF609 Knockdown Represses the Development of Non-Small Cell Lung Cancer via miR-623/FOXM1 Axis

“…12 In addition, miR-623 could repress cell proliferation and invasion via decreasing X-ray repair 1036 cross complementing 5 (XRCC5) in hepatocellular carcinoma. 13 These reports all indicated the anti-tumor role of miR-623 in many cancers. Importantly, Wei et al reported that miR-623 could reduce cell proliferation and metastasis via decreasing Ku80 in lung adenocarcinoma, a major type of NSCLC.…”

“…10 MiR-623 has been reported that could reduce tumor growth and metastasis in human cancers, such as gastric cancer, pancreatic cancer and hepatocellular carcinoma. [11][12][13] Moreover, miR-623 could repress NSCLC progression via targeting Ku80 and inactivating the extracellular signal-related kinase (ERK)/c-Jun N-terminal kinase (JNK) pathway. 14 Nevertheless, whether miR-623 is required for circZNF609 in NSCLC development is unclear.…”

CircANTXR1 Contributes to the Malignant Progression of Hepatocellular Carcinoma by Promoting Proliferation and Metastasis

“…31 High XRCC5 expression had been confirmed to promote HCC proliferation and metastasis, and could predict patients' poor prognosis. 32,33 Our data At present, the role of exosomes in cancer has received more and more attention, and exosomal circRNAs have shown great advantages in the treatment and diagnosis of cancer. 20 In this, we found that circANTXR1 was expressed in exosomes from HCC cells, and the overexpressed exosome circANTXR1 promoted HCCLM3 cell proliferation and metastasis.…”