Myc target gene, long intergenic noncoding RNA, Linc00176 in hepatocellular carcinoma regulates cell cycle and cell survival by titrating tumor suppressor microRNAs

Abstract

Hepatocellular carcinoma (HCC) is a frequent form of cancer with a poor prognosis and with limited possibilities for medical intervention. Recent evidence has accumulated that long noncoding RNAs (lncRNAs) are important regulators of disease processes including cancer. Chromatin remodeling in cancer cells may result in an unusual expression of lncRNAs and indeed it has been shown that more than 7000 unannotated lncRNAs are expressed in HCCs. We identified a novel long intergenic noncoding RNA, Linc00176, that plays a role in proliferation and survival of HCC. Linc00176 regulates expression of more than 200 genes by the sponge function for tumor suppressor miRNAs, miR-9 and miR-185. Linc00176 is expressed at a high level only in HCC, and is activated by Myc, Max and AP-4 transcription regulators. Myc also upregulates miR-9 and miR-185. In Linc00176-depleted HCC, these miRNAs were released from Linc00176 and downregulated their target mRNAs. Thus, depletion of Linc00176 disrupted the cell cycle and induced necroptosis in HCC via released tumor suppressor miRNAs. These data indicate that atypically expressed lncRNAs may be useful targets for cancer therapy.

Targeting YAP1/LINC00152/FSCN1 Signaling Axis Prevents the Progression of Colorectal Cancer

“…[5] In recent years, noncoding RNA was considered as a kind of therapeutic targets for tumors. [5] In recent years, noncoding RNA was considered as a kind of therapeutic targets for tumors.…”

“…[4] Since lncRNAs regulate a subset of genes, and are transcriptionally regulated by a series of transcription factors, targeting these lncRNAs induces a much greater effect on cancer cells than targeting single gene. [5] Therefore, exploring the upstream and downstream regulation mechanism of cancer-associated lncRNAs has been gaining widespread attention.As the main effector of the Hippo pathway, Yes-associated protein 1 (YAP1) plays a key role in regulating multiple biological function, including cell-cell contact inhibition, proliferation, and differentiation. [6,7] As a transcription coactivator, YAP1 is abnormally expressed in various malignancies, [8,9] and modulates biological phenotypes of cancer cells via regulating a number of target genes, such as CTGF, CYR61, and AREG.…”

“…[4] Since lncRNAs regulate a subset of genes, and are transcriptionally regulated by a series of transcription factors, targeting these lncRNAs induces a much greater effect on cancer cells than targeting single gene. [5] Therefore, exploring the upstream and downstream regulation mechanism of cancer-associated lncRNAs has been gaining widespread attention.…”

Knockdown of long non‐coding RNA LINC00176 suppresses ovarian cancer progression by BCL3‐mediated down‐regulation of ceruloplasmin

“…9 In consistency with our results, LINC00176 expression has been found to be expressed at high levels in hepatocellular carcinoma while depleted LINC00176 can induce necroptosis. 8 To assess the involvement of LINC00176 in the biological behaviours of ovarian cancer cells, we treated HO8910 cells with si-LINC00176. Consequently, depletion of LINC00176 in HO8910 cells significantly induced cell apoptosis and inhibited cell proliferation, migration and invasion.…”

“…LINC00176 is highly expressed in hepatocellular carcinoma while depleted expression LINC00176 can impede proliferation and induce necroptosis, highlighting that reduced expression of lncRNAs may be beneficial for cancer therapy. 8 In addition, LINC00176 associates with the survival condition of patients suffering from oesophageal cancer. 9 Based on the results from the LncMAP website, it was evident that LINC00176 could regulate the expression of ceruloplasmin (CP) via transcription factor B-cell CLL/ lymphoma 3 (BCL3).…”