Upregulating microRNA-373-3p promotes apoptosis and inhibits metastasis of hepatocellular carcinoma cells

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the digestive system. Abnormal miR-373-3p and TFAP4 expressions are critical in many malignant tumors, but it is unclear whether they work in the context of HCC. qRT-PCR measured miR-373-3p expression in HCC tissues and adjacent normal tissues. Flow cytometry and Western blot analyzed cell apoptosis. EMT, Transwell, and wound healing assay examined HCC cell migration and EMT, respectively. Western blot determined the profile of TFAP4/PI3K/AKT. IHC detected Ki67, E-cadherin, and vimentin in the tumor tissues. Moreover, the downstream target of miR-373-3p was predicted using the database. Dual luciferase activity assay and RIP verified the binding correlation between TFAP4 and miR-373-3p. In HCC tissues and cell lines, miR-373-3p was downregulated, and its overexpression stepped up HCC cell apoptosis and suppressed migration and EMT. Furthermore, miR-373-3p overexpression elevated Bax and caspase 3 expressions and attenuated Bcl2’s level. A xenograft tumor experiment in nude mice unveiled that miR-373-3p overexpression dampened tumor growth and proliferation. miR-373-3p cramped PI3K/AKT pathway activation. miR-373-3p negatively modulated TFAP4, and TFAP4 overexpression inverted miR-373-3p-mediated anti-tumor effects. Additionally, TFAP4 enhanced IGF1 expression, and promoted IGF1R-PI3K/AKT pathway activation. Collectively, miR-373-3p functions as an anti-tumor gene in HCC by inhibiting TFAP4/PI3K/AKT pathway.

Vacuolar protein sorting-associated protein 72 homolog (VPS72) binding to lysine acetyltransferase 5 (KAT5) promotes the proliferation, invasion and migration of hepatocellular carcinoma through regulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway

“…In addition, KAT5 knockdown specifically inhibits the proliferation of gallbladder carcinoma (GBC)-SD cells by casp9-mediated apoptosis [ 28 ]. Some researches claimed that the activation of PI3K/AKT signaling pathway has been implicated in the pathogenesis of hepatocellular carcinoma [ 29 , 30 ]. A case here is that maternally expressed gene 3 promotes hepatocellular carcinoma by activating PI3K/AKT signaling pathway through regulating AP1G1 [ 31 ].…”

Polysaccharides Extracted from Angelica sinensis (Oliv.) Diels Relieve the Malignant Characteristics of Glioma Cells through Regulating the MiR-373-3p-Mediated TGF-β/Smad4 Signaling Pathway

“…e findings showed that ASP dose-dependently boosted the miR-373-3p level in glioma cells. MiR-373-3p is a specific miRNA that plays a dual role in different types of cancers [15][16][17][18][19][20][21][22]. miR-373 expression has been shown to be reduced in glioma tissues, which is associated with WHO grade, KPS score, poor overall survival, and progression-free survival [23].…”

“…MiR-373-3p is an oncomiRNA that is upregulated in diverse cancers, for instance, lung adenocarcinoma [15], tongue squamous cell carcinoma [16], testicular germ cell tumor [17], and esophageal squamous cell carcinoma [18]. On the contrary, miR-373-3p can also act as an antioncomiRNA in pancreatic carcinoma [19], choriocarcinoma [20], hepatocellular carcinoma [21], cervical carcinoma [22], and glioma [23][24][25]. Jing et al proved that the miR-373 level is reduced in glioma tissues [23].…”

Modulation of AKT Pathway-Targeting miRNAs for Cancer Cell Treatment with Natural Products

“…miR-107 overexpression causes antiproliferative effects and apoptosis in hypopharyngeal cancer cells through the inactivation of PI3K/AKT [ 49 ]. miR-373-3p is downregulated [ 51 ] and transcription factor-activating enhancer-binding protein 4 (TFAP4) is upregulated [ 65 ] in liver cancer tissues. TFAP4 activates PI3K/AKT expression [ 65 ].…”

“…TFAP4 activates PI3K/AKT expression [ 65 ]. Upregulating miR-373-3p triggers apoptosis in liver cancer cells by downregulating AKT and TFAP4, which is reversed by TFAP4 overexpression [ 51 ]. miR-1306-5p is downregulated in colon cancer cells and tissues [ 53 ].…”