lncRNA RMRP knockdown suppress hepatocellular carcinoma biological activities via regulation miRNA‐206/TACR1

Abstract

Long noncoding RNA, RNA component of mitochondrial RNA processing endoribonuclease (RMRP) plays an important role in cancer development and is closely correlated with prognosis in cancer patients. However, whether RMRP affects prognosis in patients with hepatocellular carcinoma (HCC) remains unclear. The aim of the present study was to investigate the expression level of RMRP in HCC and its correlation with prognosis in patients with HCC and explain the effects and associated mechanisms by conducting an in vitro study. The high expression level of RMRP was correlated with poor prognosis in patients with HCC. Using in vitro analysis, RMRP knockdown suppressed HCC cell proliferation, invasion, and migration (P < .05). miRNA‐206 overexpression had similar effects in HCC cell lines (Bel‐7402 and Huh‐7). Using Western blot analysis and cellular immunofluorescence detection, RMRP downregulation significantly suppressed TACR1/Erk1/2 pathway, while miRNA‐206 was significantly upregulated (P < .05). RMRP downregulation inhibits HCC‐related biological activities by the regulation of miRNA‐206/TACR1.

<p>The Hsa_circ_0091579/miR-940/TACR1 Axis Regulates the Development of Hepatocellular Carcinoma</p>

“…A previous study suggested that TACR1 functioned as an oncogene in HCC development. 20 In our study, TACR1 expression was enhanced in HCC, indicating the potential carcinogenic role of TACR1 in HCC. Moreover, we identified the oncogenic role of TACR1 in HCC by reversing the anticancer function of miR-940, which was also similar to that in neuroblastoma.…”

“…16,17 The tachykinin-1 receptor (TACR1) has been suggested to be an oncogene in many malignancies, including HCC. [18][19][20] The bioinformatics analysis using CircInteractome 21 and TargatScan 22 predicts that miR-940 could bind with circ_0091579 and TACR1. However, it is not clear whether miR-940 and TACR1 are associated with circ_0091579mediated HCC development.…”

RNA polymerase III transcription as a disease factor

“…Elevated levels of RMRP have been observed in different cancers, in one case as a result of transcriptional activation of the RMRP gene by the Wnt pathway through binding of YAP and β-catenin to the TATA box of the RMRP promoter (Park and Jeong 2015). High RMRP expression has been associated with poor patient prognosis and consistent with this, RMRP knockdown and overexpression experiments in various cancer cell lines revealed a positive role in cell proliferation and tumorigenic potential (Meng et al 2016;Shao et al 2016;Cao et al 2019;Hongfeng et al 2019;Pan et al 2019;Tang et al 2019;Wang et al 2019a,b;Xiao et al 2019).…”

“…Overexpression of RMRP in lung adenocarcinoma cells led to decreased levels of miR-206 and, in turn, increased levels of the miR-206 targets KRAS, FMNL2, and SOX9 (Meng et al 2016). In neuroblastoma and hepatocellular carcinoma cells, decreased miR-206 levels linked to RMRP overexpression led to elevated TACR1, which in turn activated ERK1/2 signaling (Hongfeng et al 2019;Pan et al 2019). A negative correlation between RMRP and miR-206 levels was also observed in bladder cancer (Cao et al 2019).…”

Long Noncoding RNAs Coregulated by Annexin A7 and JNK in Hepatocellular Carcinoma Cells Identified by Whole-Genome Expression Profiling

“…Long noncoding RNAs (lncRNAs) are 200-nt or more transcripts that do not encode proteins but regulate coding gene expression, thereby influencing many diverse biological processes including disease pathogenesis [24][25][26][27]. Dysregulated expression of HCC-related lncRNAs such as MEG-3 [28], MALAT1 [29], HULC [30], HOTAIR [31], and H19 [32] have been linked to tumorigenesis and metastasis.…”