LncRNA PITPNA-AS1 as a Potential Diagnostic Marker and Therapeutic Target Promotes Hepatocellular Carcinoma Progression via Modulating miR-448/ROCK1 Axis.

Qing-Fang Wang,Ming-Bo Cao,Qing-Lin Wang

doi:10.3389/fmed.2021.668787

Qing-Fang Wang, Ming-Bo Cao + Show 1 more

Open Access

https://doi.org/10.3389/fmed.2021.668787

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Abstract

Background: Long non-coding RNAs are critical to hepatocellular carcinoma (HCC) developments. LncRNA PITPNA antisense RNA 1 (PITPNA-AS1) is a new regulator in several tumors. However, the mechanism by which PITPNA-AS1 mediates the tumorigenesis of HCC remains unclear.Methods: RT-qPCR was used to detect the level of PITPNA-AS1 in HCC specimens and cells. The biological functions of PITPNA-AS1 were explored by several functional experiments in vivo and in vitro. The binding relationship among PITPNA-AS1, miR-448 and ROCK1 were studied by Luciferase assay and pull-down assays.Results: We found that PITPNA-AS1 expressions were distinctly upregulated in both HCC specimens and cell lines. High PITPNA-AS1 levels were an unfavorable biomarker for patients with HCC. Functionally, knockdown of PITPNA-AS1 suppressed the proliferation, migration and invasion of HCC cells. Mechanistically, PITPNA-AS1 functioned as competing endogenous RNA to increase ROCK1 expressions via sponging miR-448.Conclusion: The newly identified PITPNA-AS/miR-448/ROCK1 axis promoted the oncogenicity of HCC cells. This novel axis is likely to be a promising HCC therapeutic aim.

Highlights

Hepatocellular carcinoma (HCC) is a common malignancy worldwide and the second leading cause of cancer-related death [1]
We found a lncRNA, PITPNA-AS1 which was distinctly overexpressed in HCC specimens from TCGA datasets (Figure 1A)
Based TCGA datasets, patients with high PITPNAAS1 showed a shorter overall survival than those with low PITPNA-AS1 expression (Figure 1D). These results highlighted the involvements of PITPNA-AS1 in HCC progression

Summary

Introduction

Hepatocellular carcinoma (HCC) is a common malignancy worldwide and the second leading cause of cancer-related death [1]. Even though effective surgical technique and diagnostic processes have resulted in the distinct improvements of clinical outcome of HCC patients, the long-term survivals are still unsatisfactory largely due to positive metastasis and the high recurrence (45–65% at 5 years) [3, 4]. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides [5]. According to a growing volume of literature, the dysregulation of lncRNAs was frequent in various tumors and involved in tumor progression [7, 8]. The expression and underlying mechanism of HCC associated with aberrant lncRNAs remain largely unclear. Long non-coding RNAs are critical to hepatocellular carcinoma (HCC) developments. The mechanism by which PITPNA-AS1 mediates the tumorigenesis of HCC remains unclear

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Results

Conclusion