Role of long intergenic non-protein coding RNA 01857 in hepatocellular carcinoma malignancy via the regulation of the microRNA-197-3p/anterior GRadient 2 axis.

Jiangang Bi,Liping Liu,Shiyun Bao,Qi Li,Ping Xu,Yusheng Guo,Olorunseun Ogunwobi

doi:10.1371/journal.pone.0258312

Jiangang Bi, Liping Liu + Show 5 more

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https://doi.org/10.1371/journal.pone.0258312

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Abstract

This study investigates the differential expression and the mechanism of long intergenic non-protein coding RNA (LINC) 01857 in hepatocellular carcinoma (HCC) proliferation and apoptosis. LINC01857 expression in HCC tissues and cells was evaluated. In addition, gain-of and loss-of functions were carried out to assess HCC cell proliferation and apoptosis. After that, LINC01857 subcellular localization was predicted and verified. Additionally, the binding relations between LINC01857 and microRNA (miRNA)-197-3p and between miR-197-3p and anterior GRadient 2 (AGR2) were detected and confirmed. Besides, HCC cell proliferation and apoptosis were assessed after silencing LINC01857 or overexpressing AGR2. Next, levels of key factors in the AKT and ERK pathways were measured. Additionally, xenograft transplantation was also conducted to confirm the effect of LINC01857 in HCC. LINC01857 was overexpressed in HCC. Silencing LINC01857 leads to a blockage in HCC cell proliferation but improved apoptosis. LINC01857 could competitively bind to miR-197-3p and thus upregulate AGR2. miR-197-3p was poorly expressed in HCC, while AGR2 was overexpressed. Mechanistically, downregulated miR-197-3p or overexpressed AGR2 were observed to attenuate the effect of the LINC01857 knockdown on suppressing cell proliferation and enhancing apoptosis. Moreover, LINC01857 activated the AKT and ERK pathways through the manipulation of the miR-197-3p/AGR2 axis in HCC. The results of this study indicated that LINC01857 was highly expressed in HCC, and it could improve HCC cell proliferation and reduce apoptosis via competitively binding to miR-197-3p, promoting AGR2 and upregulating the AKT and ERK pathways.

Highlights

Hepatocellular carcinoma (HCC) refers to a prevalent and lethal carcinoma classified under chronic hepatic disorders that leads to an unfavorable prognostic aftermath and high mortality [1, 2]
LINC01857 could competitively bind to miR-1973p and upregulate anterior GRadient 2 (AGR2). miR-197-3p was poorly expressed in HCC, while AGR2 was overexpressed
The results of this study indicated that LINC01857 was highly expressed in HCC, and it could improve HCC cell proliferation and reduce apoptosis via competitively binding to miR197-3p, promoting AGR2 and upregulating the AKT and extracellular signal-regulated kinase (ERK) pathways

Summary

Introduction

Hepatocellular carcinoma (HCC) refers to a prevalent and lethal carcinoma classified under chronic hepatic disorders that leads to an unfavorable prognostic aftermath and high mortality [1, 2]. As a complicated tumor with heterogeneity, HCC accounts for almost 90% of primary liver neoplasms has emerged as a challenging dilemma and health burden worldwide [3]. HCC is a unique cancer that typically arises from chronic liver disease, and its incidence rate depends on the complex interaction among the host, disease and environmental factors, and chronic hepatitis B or C virus infection is the main risk factor worldwide [4]. Regarding advanced therapies, curable therapies are inaccessible and might cost a large amount of expenditure but just exert little efficiency on prognosis and overall survival rate [6]. Against this backdrop, acquaintance with the potential crosstalk in HCC is of increasing importance

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