Abstract 3715: Long-chain non-coding RNA H19-miR-152-3p axis regulates AFP expression in hepatocellular carcinoma
Authors: Ke Yang , Kui Xiang , Jiang Hang , Wu Tiangen , Zhang Cheng , Zhou Jian , Li Jinze , Zhang Heng , Song Yueqiang , Zhao Juan , Duan Huafeng , Wang Lin , Wang Yan 
Published: September 2020

Background:

Serum alpha-fetoprotein (AFP) is the most widely used serological marker used to diagnose hepatocellular carcinoma (HCC). High expression of AFP is significantly associated with early postoperative recurrence and poor prognosis. However, the upstream regulation mechanism of AFP expression is not fully understood, and the role of long-chain non-coding RNA (lncRNA) in AFP expression regulation has not been reported.

Methods:

HCC cases from The Cancer Genome Atlas (TCGA) database were divided into 3 groups: (1) AFP&lt;10ng/ml, (2) 10ng/ml≤AFP&lt;1000ng/ml, and (3) AFP≥1000ng/ml. The differential expression and co-expression of lncRNAs and miRNAs with AFP among the 3 groups was analyzed. lncRNA-ceRNA for AFP expression regulation was constructed by using LncATLAS to predict lncRNAs localization, miRWalk3.0 to predict miRNA-AFP targets, and LncBase Predicted v.2 to predict miRNA-lncRNA targets.

Results:

In the 3 groups, 32 lncRNAs were differentially expressed (P&lt;0.05). SNHG7, SNHG3, SNHG8, DSCR9, KCNQ1OT1, SNHG6, GAS5, SNHG11, H19, TMEM191A, and MEG3 were significantly positively correlated with AFP expression (r&gt;0, P&lt;0.05). SEC22B and SRD5A2 were significantly negatively correlated with AFP expression (r&lt;0, P&lt;0.05). Among the positively correlated lncRNAs, SNHG7, SNHG3, SNHG8, SNHG6, GAS5, and H19 were mainly located in the HepG2 cytoplasm, DSCR9, KCNQ1OT1, SNHG11, and MEG3 were mainly located in the HepG2 nucleus, and TMEM191A had no location information in HepG2 cells. We found 134 differentially expressed miRNAs (P&lt;0.05), and hsa-miR-196a-5p, hsa-miR-18a-5p, hsa-miR-148b-3p, hsa-miR-483-5p, hsa-miR-1307-3p, hsa-miR-1301-3p, hsa-miR-222-5p, hsa-miR-18a-3p, hsa-miR-501-5p, hsa-miR-483-3p, hsa-miR-222-3p, hsa-miR-19a-3p, and hsa-miR-221-3p were significantly positively correlated with AFP expression (r&gt;0, P&lt;0.05). hsa-miR-99a-5p, hsa-miR-152-3p, hsa-miR-125b-2-3p, hsa-let-7c-5p, and hsa-miR-1295b-5p were significantly negatively correlated with AFP expression (r&lt;0, P&lt;0.05). Among the negatively correlated miRNAs, hsa-miR-152-3p, hsa-miR-125b-2-3p, and hsa-let-7c-5p were predicted to be able to target the AFP 3' UTR. LncRNAs were predicted for the 3 miRNAs mentioned above. At the LncBase score&gt;0.60, 769 pairs of miRNA-lncRNA interaction were recognized. These predicted lncRNAs were then intersected with the 6 cytoplasm-located lncRNAs. H19 satisfied the constraints, and therefore, a lncRNA H19-miR-152-3p-AFP ceRNA was proposed.

Conclusions:

Our study revealed that the proposed H19-miR-152-3p-AFP pathway affects the expression of AFP in HCC, suggesting that the H19-miR-152-3p axis may play an important role in the development of typical AFP-positive HCC.

Citation Format: Yang Ke, Xiang Kui, Hang Jiang, Tiangen Wu, Cheng Zhang, Jian Zhou, Jinze Li, Heng Zhang, Yueqiang Song, Juan Zhao, Huafeng Duan, Lin Wang, Yan Wang. Long-chain non-coding RNA H19-miR-152-3p axis regulates AFP expression in hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3715.