LncRNA LINC00667 aggravates the progression of hepatocellular carcinoma by regulating androgen receptor expression as a miRNA-130a-3p sponge

Zhixiang Qin,Hai Yang,Zijing Li,Xiaohong Liu,Zhe Feng,Ganggang Wang,Zidong Zhang,Ye Liu,Kun Li,Chengpeng Tan

doi:10.1038/s41420-021-00787-4

Abstract

Emerging studies have found long noncoding RNAs, widely expressed in eukaryotes, crucial regulators in the progression of human cancers, including hepatocellular carcinoma (HCC). Although the long intergenic noncoding RNA 667 (LINC00667) can promote the progression of a variety of cancer types, the expression pattern, the role in cancer progression, and the molecular mechanism involved in HCC remain unclear. This study aims to investigate the function and mechanism of LINC00667 in HCC progression. The effects of LINC00667 silencing in cell proliferation, cell migration, and cell invasion, and androgen receptor (AR) expression were determined with loss-of-function phenotypic analysis in Huh-7 and HCCLM3 cells, and subsequently testified in vivo in tumor growth. We found that the expression of LINC00667 was upregulated in HCC tissues and cell lines. Upregulation of LINC00667 was significantly associated with the unfavorable prognosis of HCC in our study patients. On the other hand, low expression of LINC00667 significantly inhibited the cell proliferation, cell migration and cell invasion of HCC in vitro and tumor growth in vivo. This inhibitory effect could be counteracted by miR-130a-3p inhibitor. LINC00667 reduced the inhibition of AR expression by miR-130a-3p, which correlated with the progression of HCC. Our finding suggests LINC00667 is a molecular sponge in the miR-130s-3p/AR signal pathway in the progression of HCC, in which it relieves the repressive function of miR-130a-3p on the AR expression. This indicates LINC00667 functions as a tumor promotor in promoting HCC progression through targeting miR-130a-3p/AR axis, making a novel biomarker and potential therapeutic target for HCC.

Highlights

Hepatocellular carcinoma (HCC) is a common malignancy of the digestive system, especially in the developing world
MiRNA-130a-3p is downregulated in HCC tissues and suppresses cell proliferation (CP), cell metastasis (CM) and cell invasion (CI) in HCC cells Considering that LINC00667 is localized in the cytoplasm and based on the concept of competing endogenous RNA, we further investigated whether LINC00667 can promote the malignant behavior of HCC tissues by acting as miRNA sponges [29]
Long noncoding RNAs are involved in the biological process of various tumors, including HCC

Summary

Introduction

Hepatocellular carcinoma (HCC) is a common malignancy of the digestive system, especially in the developing world. Further exploration of the molecular mechanism of HCC and the development of more effective treatment strategies are of utmost urgency. Long noncoding RNA (lncRNA) is a class of nonprotein-coding RNAs (>200 nt) that have multiple functions such as participating in protein translation, interacting with RNA-binding protein (RBP) and acting as a miRNA sponge [2,3,4,5]. Long intergenic noncoding RNA 667 (LINC00667) is a cancer-related lncRNA, and its abnormal expression levels have been widely reported in various kinds of cancers including cholangiocarcinoma [10], nephroblastoma [11], and esophageal cancer [12]. The exact molecular mechanisms of LINC00667 in HCC remain largely unknown

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