miR-302a inhibits human HepG2 and SMMC-7721 cells proliferation and promotes apoptosis by targeting MAP3K2 and PBX3

Abstract

Hepatocellular carcinoma (HCC) is the most common liver cancer and has a poor prognosis. miR-302a is an important regulator of tumor occurrence and deterioration, while MAP3K2 and PBX3 genes are involved in cancer cell proliferation and apoptosis. In this study, the expression of miR-302a and MAP3K2/PBX3 were evaluated by qPCR in liver cancer cell lines. Next, the target relationship between miR-302a and MAP3K2/PBX3 was verified using luciferase assays. Meanwhile, the expression correlation between miR-302a and target genes was analyzed in cancer tissue and para-cancerous tissue. In addition, an increased miR-302a level in HepG2 cells and SMMC-7721 cells were achieved through transfection with miR-302a mimics, and the effects on HepG2 cell and SMMC-7721 cell proliferation, apoptosis and MAPK pathways were determined using MTT, flow cytometry, qPCR and western blot assays. The results showed that liver cancer cell lines exhibited low miR-302a expression and MAP3K2 and PBX3 were confirmed to be the target genes of miR-302a. Meanwhile, the HE results showed that cells became enlarged with loose cytoplasm and formed balloon-like lesions in HCC specimens and we found a significant negative correlation between miR-302a and MAP3K2/PBX3 expression. In addition, treatment with miR-302a mimics inhibited HepG2 cells and SMMC-7721 cells proliferation and increased the apoptosis rate. Further research revealed that the MAPK key factors p-p38, p-ERK1/2 and p-JNK were significantly reduced in miR-302a transfected cells and MAP3K2/PBX3 silenced cells. Besides, MAP3K2 and PBX3 overexpression in miR-302a mimics-treated cells exerted the opposite effects. In conclusion, miR-302a inhibited proliferation and promoted apoptosis in human hepatoma cells by targeting MAP3K2 and PBX3.

MG132 inhibits the expression of PBX3 through miRNAs by targeting Argonaute2 in hepatoma cells

“…HCC is one of the most prevalent malignancies and the leading cause of cancer-related deaths worldwide ( Wang et al, 2019 ). Local recurrence and distant metastasis often result in poor prognosis ( Ringehan et al, 2017 ).…”

miR-126 targeting GOLPH3 inhibits the epithelial-mesenchymal transition of gastric cancer BGC-823 cells and reduces cell invasion

“…miRNAs are abnormally expressed in tumors and play a role either as oncogenes or tumor suppressor genes in tumor progression. 14 Some studies have compared nine gastric cancer cell lines detected by the miRNAs microarray with normal gastric tissues, and miR-126 was significantly downregulated. 15 Yue et al also found that miR-126 expression in gastric cancer tissues decreased significantly, and in vitro gastric cancer cells could inhibit the growth of SGC7901 cells by inducing the G0/G1 phase to block the cell cycle.…”

PBX3 in Cancer

“…There is also evidence that an additional miR, miR-320a, can be transferred to HCC cells from neighboring cancer-associated fibroblasts (CAFs) via exosomes. Once in HCC cells, miR-320a can block proliferation and migration through inhibition of EMT, as well as cyclin-dependent kinase 2 (CDK2) and MMP2 [27], and (from a later study) MAP3K2 [34].…”

“…The first report of a PBX3-specific miR was published in 2011, when Ramberg et al demonstrated that the miR-let-7d repressed PBX3 expression in prostate cancer [14], and this was followed shortly after by a report that the closely related miR-let-7c was complementary to the 3'UTR of PBX3 and could directly repress its expression in colorectal cancer [17], as could miR-let-7b in glioma [18]. Subsequently, PBX3 expression was also shown to be reduced by miR-181 in AML [19], miR-129-5p in pancreatic cancer [20], miR-495 in AML [21] and melanoma [22], miR-200b in breast cancer [23], miR-200b, miR-222, and miR-424 in hepatocellular carcinoma (HCC) [24], miR-320a in multiple myeloma [25], gastric cancer [26], and cancer-associated fibroblasts (CAFs) associated with HCC [27], miR-33a-3p in HCC [28], miR-497 in multiple myeloma [29], miR-144-3p in gastric cancer [30], miR-98 in glioma [31], miR-144 in lung cancer [32] and HCC [33], miR-302a in HCC [34], and miR-526b in cervical cancer [35]. In addition, within the context of early development, miR-320 was shown to maintain the undifferentiated state in chick blastodermal cells through repression of PBX3 [5].…”

“…Prostate cancer Upregulated by androgen [14] miR-let-7c Colorectal cancer Binds 3'UTR, also targets MMP11 [17] miR-let-7b Glioma Binds 3'UTR [18] miR-181 AML Binds 3'UTR [19] miR-129-5p Pancreatic cancer Binds 3'UTR [20] miR-495 AML and melanoma Binds 3'UTR, also targets MEIS1 [21] miR-200b HCC and breast cancer Binds 3'UTR [23,24] miR-222 HCC Binds 3'UTR [24] miR-424 HCC Binds 3'UTR [24] miR-320a MM, gastric cancer, and HCC Binds 3'UTR [25][26][27] miR-33a-3p HCC Binds 3'UTR [28] miR-497 MM Binds 3'UTR [29] miR-144-3p Gastric cancer Binds 3'UTR [30] miR-98 Glioma Binds 3'UTR [31] miR-144 Lung cancer, HCC Binds 3'UTR, also binds the lncRNA UCA1 [32,33] miR-302a HCC Binds 3'UTR, also targets MAP3K2 [34] miR-526b Cervical cancer Binds 3'UTR [35] Author…”