Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐Met

Abstract

Hematologic and neurological expression 1 (HN1) has been reported to involved in certain cancers, but its role in hepatocellular carcinoma (HCC) is largely unknown. The contribution of HN1 to HCC progression was investigated in the present study. We found that HN1 was significantly up‐regulated in HCC tissues, compared with normal tissues, by analyzing the Oncomine and Human Protein Atlas database; and found that high expression of HN1 was markedly associated with worse overall survival, relapse‐free survival, progression‐ free survival and disease‐specific survival in HCC patients via exploring the Kaplan‐Meier plotter database. Functional assays revealed that HN1 knockdown by siRNA induced G1 cell cycle arrest, and inhibited the growth and migration of HCC cells; accordingly, HN1 over‐expression promoted HCC cells proliferation and migration. Further studies indicated that HN1 knockdown reduced the expression of cyclin D1 and CDK4, while upregulated the cell cycle inhibitor p21WAF1/Cip1. Moreover, HN1 knockdown decreased c‐Met (receptor tyrosine kinase of hepatocyte growth factor) expression, and suppressed ERK activation, which is a common downstream signaling pathway triggered by c‐Met; consistently, HN1 over‐expression reversed these effects. Meanwhile, down‐regulation of c‐Met partly eliminated the effect of HN1 over‐expression in HCC cells. Thus, the present findings suggested that HN1 promotes the progression of HCC to some extent by up‐regulating the expression of c‐Met, and may act as a potential biomarker and therapeutic target for the treatment of HCC.

CircHN1 affects cell proliferation and migration in gastric cancer

“…CircHN1 is formed by reverse splicing of the linear transcript of exons 3‐5 of HN1 gene. HN1 mRNA has been shown to be upregulated in certain cancers 21‐24 . Increased HN1 expression has been reported to upregulate c‐Met to promote cell growth and migration and is linked to a poor prognosis for patients with hepatocellular carcinoma (HCC) 21 .…”

“…HN1 mRNA has been shown to be upregulated in certain cancers 21‐24 . Increased HN1 expression has been reported to upregulate c‐Met to promote cell growth and migration and is linked to a poor prognosis for patients with hepatocellular carcinoma (HCC) 21 . In breast cancer, HN1 can enhance MYC expression to contribute to cancer progression 22 .…”

Downregulation of circular RNA circ-HN1 suppressed the progression of gastric cancer through the miR-485-5p/GSK3A pathway

“…Ding et al ( 16) have revealed that circ-DONSON is upregulated in tumor tissues and its knockdown restrains cell proliferation, migration, and invasion in GC. The expression of the HN1 gene is commonly elevated in tumors and contributes to accelerated tumor progression in breast cancer, anaplastic thyroid carcinoma, prostate cancer, and hepatocellular carcinoma (17)(18)(19)(20). CircHN1, encoded by the HN1 gene, can promote proliferation, migration, and invasion, as well as inhibit apoptosis in GC (11,12).…”

Angiogenesis-related non-coding RNAs and gastrointestinal cancer

“…289 HN1 was correlated with a poor prognosis in HCC patients. 290 Pu et al 291 294 Moreover, bioinformatic approaches and various databases have enabled the discovery of thousands of novel ncRNAs in cancers, including GI cancer. These databases include CRlncRNA, Lnc2Cancer, and LncRNADisease.…”

“… 289 HN1 was correlated with a poor prognosis in HCC patients. 290 Pu et al. 291 investigated the hsa_circ_0000092 and HN1 effects on angiogenesis in HCC.…”