FOXO3-induced lncRNA LOC554202 contributes to hepatocellular carcinoma progression via the miR-485-5p/BSG axis
Authors: Hai-Juan Xiao
Bao-Guo Zhao
Yu Fang
Wan-Li Deng
Yao Xu
Xiao-Wen Wang
Lin Yang
Journal: Cancer Gene Therapy (2021)
Discipline: CLINICAL MEDICINE
Keywords: Long non-coding RNAs; LncRNAs; hepatocellular carcinoma; HCC; LOC554202
Affiliations: Department of Hepatobiliary Surgery, The Xianyang Central Hospital, Xianyang, Shaanxi, China., Department of Oncology, The Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Putuo, Shanghai, China., Department of Oncology, The Affiliated Hospital of the Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, China., Department of Oncology, The Affiliated Hospital of the Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, China. .

Abstract:  Long non-coding RNAs (LncRNAs) have played very important roles in the malignancy behaviors of hepatocellular carcinoma (HCC). LncRNA LOC554202 (LOC554202) was a newly identified tumor-related lncRNA. However, its expression and function in HCC remained unknown. In this study, we firstly reported that LOC554202 expression was distinctly upregulated in HCC specimens and cell lines. Clinical assays indicated that increased LOC554202 expression had a diagnostic value for HCC patients and was positively associated with advanced stages and poor clinical prognosis. Additionally, forkhead box O3(FOXO3) could bind directly to the LOC554202 promoter region and activate its transcription. Functionally, we observed that knockdown of LOC554202 suppressed the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) progress of HCC cells, and promoted apoptosis. Mechanistically, LOC554202 competitively bound to miR-485-5p and prevented the suppressive effects of miR-485-5p on its target gene basigin (BSG), which finally led to HCC metastasis, EMT, and docetaxel chemoresistance. Our data demonstrated that FOXO3-induced LOC554202 contributed to HCC progression by upregulating BSG via competitively binding to miR-485-5p, which suggested that the regulation of the FOXO3/LOC554202/miR-485-5p/BSG axis may have beneficial effects in the treatment of HCC. 

Retracted: No

PubPeer comments:
 This study relies on the ability to accurately quantitate certain transcripts by quantitative PCR, but the methods are missing and I have concerns about the indicated primers. No methods are given for qPCR. Instead, a reference (ref 23) is made to Jiang, et al, Aging, 2020, Identification of HMG-box family establishes the significance of SOX6 in the malignant progression of glioblastoma (PMID: 32388501). Unfortunately, Jiang et al do not perform qPCR of any kind. Their study is purely in silico. Could the authors please provide the full qPCR methods for both long and short RNAs? microRNAs like miR-485-5p are too short to be amplified directly, so they require a special reverse transcription process before qPCR. If an appropriate RT step has been done, the forward primer for a mature miRNA is usually identical to the whole miRNA or a part of it. The sequence of miR-485-5p is AGAGGCUGGCCGUGAUGAAUUC. Here, the primers are given as miR-485-5p F: CCAAGCTTCACCCATTCCTAACAGGAC and miR-485-5p R: CGGGATCCGTAGGTCAGTTACATGCATC. It does not appear that these primers would recognize any part of mature miR-485-5p.I hope that the authors can indicate exactly how miR-485-5p with these apparently unrelated primers. I have not checked the other primers and sequences, but I would recommend that the authors do so. ,