LncRNA HOTAIRM1 inhibits the progression of hepatocellular carcinoma by inhibiting the Wnt signaling pathway
Authors: L Mi
C Gao
Y Zhang
Y-H Wang
J Liu
Y Xuan
H-X Ming
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA HOTAIRM1; hepatocellular carcinoma; apoptosis; proliferation; Wnt pathway
Affiliations: Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, China. .

Abstract:  Objective: To explore the possible role of long non-coding RNA (lncRNA) HOTAIRM1 in the pathogenesis of hepatocellular carcinoma (HCC) and its underlying mechanism. Patients and methods: LncRNA HOTAIRM1 expressions in 30 pairs of hepatocellular carcinoma tissues and paracancerous tissues were detected by quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR). The survival analysis and receiver operating characteristic (ROC) curve were introduced to explore the relationship between lncRNA HOTATRM expressions and prognosis of HCC patients. The correlation between overall survival and clinical variables of HCC patients was estimated by single-factor and multiple-factor regression analysis, respectively. Overexpression plasmid of lncRNA HOTAIRM1 was designed and transfected into HCC cells according to the instructions of Lipofectamine 2000. Cell proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Moreover, expressions of apoptosis-related genes and the Wnt pathway-related proteins were detected by Western blot. Results: Lower lncRNA HOTAIRM1 expressions were observed in the HCC tissues than those of the paracancerous tissues. ROC curve indicated a high sensitivity and specificity of lncRNA HOTAIRM1 for HCC. PFS in HCC patients was correlated with tumor size and lncRNA HOTAIRM1 expression, whereas not correlated with age, sex, GGT, AFP, Child-Pugh grade, HBsAg, cirrhosis, number of tumors, micro-vessel metastasis, tumor differentiation, and TNM stage of HCC. Overexpression of HOTAIRM1 led to decreased proliferative ability and increased apoptosis of HepG2 and HHCC cells. In addition, overexpressed lncRNA HOTAIRM1 remarkably increased the expression of apoptosis promotor Bax, but decreased the expressions of apoptosis inhibitors Bcl-2 and Bid. Meanwhile, expressions of related proteins in the Wnt pathway were decreased as well. Conclusions: HOTAIRM1, which was downregulated in HCC, might inhibit the proliferative ability and promote the apoptosis of HCC cells by suppressing the Wnt pathway, thereby inhibiting the progression of hepatocellular carcinoma. 

Retracted: No

PubPeer comments:
  Tumor tissues and the corresponding paracancerous tissues of HCC patients with surgical resection in our hospital from **July 2012 to February 2017** were collected. ...  Notably, our finding demonstrated that the survival time of HCC patients with low lncRNA HOTAIRM1 expression was significantly reduced compared with those of high expression group (p=0.0299, Figure 1D). Fig 1D.  The survival time of HCC patients with high lncRNA HOTAIRM1 expression was significantly longer than those with low expression . ![file] Figure 1D shows that patient survival was tracked for up to 10 years after recruitment, i.e. into the date range **July 2022 to February 2027**, for a 2018 paper. How does that work? , 
 Corrected [September 2021] . ---------------------- After publication, the authors found some mistakes in the article. The Publisher apologizes for any inconvenience this may cause. The correct sections are reproduced below. - In the Abstract section, the u201cprogression-free survival (PFS)u201dis not correct, it should be u201coverall survivalu201d. - In the Patient and Methods section, u201cTumor tissues and the corresponding paracancerous tissues of HCC patients with surgical resection in our hospital from July 2012 to February 2017 were collectedu201d should be u201cTumor tissues and the corresponding paracancerous tissues of HCC patients with surgical resection in our hospital from July 2002 to February 2007 were collectedu201d. - In the Results section, u201cHigher expressions of lncRNA HOTAIRM1 were observed in HCC tissues than those of the paracancerous tissuesu201d should be u201cLower expressions of lncRNA HOTAIRM1 were observed in HCC tissues than those of the paracancerous tissuesu201d. ,