Upregulation of microRNA‐140‐3p inhibits epithelial‐mesenchymal transition, invasion, and metastasis of hepatocellular carcinoma through inactivation of the MAPK signaling pathway by targeting GRN

• Published in: Journal of cellular biochemistry Vol. 120; no. 9; pp. 14885 - 14898
• Main Authors: Zhang, Qiu‐Yin, Men, Chang‐Jun, Ding, Xue‐Wei
• Format: Journal Article
• Language: English
• Published: United States 01.09.2019
• Subjects: epithelial‐mesenchymal transition; granulin; hepatocellular carcinoma; invasion and metastasis; microRNA‐140‐3p; mitogen‐activated protein kinase signaling pathway; epithelial-mesenchymal transition; mitogen-activated protein kinase signaling pathway; microRNA-140-3p; invasion and metastasis; granulin; hepatocellular carcinoma
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28750

Invasion and metastasis in hepatocellular carcinoma (HCC) results in poor prognosis. Human intervention in these pathological processes may benefit the treatment of HCC. The aim of the present study is to elucidate the mechanism of miR‐140‐3p affecting epithelial‐mesenchymal transition (EMT), invasion, and metastasis in HCC. Microarray analysis was performed for differentially expressed genes screening. The target relationship between miR‐140‐3p and GRN was analyzed. Small interfering RNA (siRNA) against granulin (GRN) was synthesized. EMT markers were detected, and invasion and migration were evaluated in HCC cells introduced with a miR‐140‐3p inhibitor or mimic, or siRNA against GRN. A mechanistic investigation was conducted for the determination of mitogen‐activated protein kinase (MAPK) signaling pathway‐related genes and EMT markers (E‐cadherin, N‐cadherin, and Vimentin). GRN was highlighted as an upregulated gene in HCC. GRN was a target gene of miR‐140‐3p. Elevation of miR‐140‐3p or inhibition of GRN restrained the EMT process and suppressed the HCC cell migration and invasion. HCC cells treated with the miR‐140‐3p mimic or siRNA‐GRN exhibited decreased GRN expression and downregulated the expressions of the MAPK signaling pathway‐related genes, N‐cadherin, and Vimentin but upregulated the expression of E‐cadherin. GRN silencing can reverse the activation of the MAPK signaling pathway and induction of EMT mediated by miR‐140‐3p inhibition. Taken together, the results show that miR‐140‐3p confers suppression of the MAPK signaling pathway by targeting GRN, thus inhibiting EMT, invasion, and metastasis in HCC. miR‐140‐3p confers suppression of the mitogen‐activated protein kinase signaling pathway by targeting granulin, thus inhibiting epithelial‐mesenchymal transition, invasion, and metastasis in hepatocellular carcinoma.