LncRNA MKRN3-AS1 promotes metastasis and autophagy of hepatocellular carcinoma by sponging multiple microRNAs
4 affiliations
- 1The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University
- 2Department of Surgery, Quanzhou Maternity and Children’s Hospital
- 3The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine
- 4Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital
Abstract
Hepatocellular carcinoma is one of the most common malignant tumors with poor clinical outcomes. Increasing numbers of long noncoding RNAs have been shown to be involved in the carcinogenesis and progression of HCC. However, the expressions, clinical significances, and roles of most lncRNAs in HCC are still unknown. In clinical samples, we utilized qPCR assays to measure the expression level of lncRNA MKRN3-AS1 in hepatocellular carcinoma (HCC) tissues compared with normal/adjacent tissues and analyzed its correlation with patient prognosis. Gain-of-function and loss-of-function experiments were performed in HCC cells to examine the effects of lncRNA MKRN3-AS1 on cell migration, invasion, and autophagy. For mechanistic investigation, bioinformatics analysis and molecular biology experiments were employed to verify the role of MKRN3-AS1 as a competitive endogenous RNA. Additionally, a mouse metastatic tumor model was established via tail vein injection to observe the impact of MKRN3-AS1 on lung metastasis of hepatocellular carcinoma. We found that lncRNA MKRN3-AS1 was dramatically upregulated in HCC tissues and associated with poor prognosis. Functionally, lncRNA MKRN3-AS1 promoted migration, invasion and autophagy of HCC cells. Mechanistically, MKRN3-AS1 acted as a “molecular sponge” for multiple miRNAs. By targeting miR-601, MKRN3-AS1 upregulate the expression of ZEB1, which directly promoted the invasion and migration of HCC cells. In addition, MKRN3-AS1 promoted autophagy via the miR-4487/ULK1 and miR-6881-3p/ATG5-ATG7 axes, which may enhance the stemness of HCC cells and thereby indirectly facilitate tumor invasion and migration. In mouse model, over-expression of MKRN3-AS1 facilitated lung metastasis of HCC. Collectively, The oncogenic function of MKRN3-AS1 in hepatocellular carcinoma may be attributed to its regulation of the miR-601/ZEB1, miR-4487/ULK1, and miR-6881-3p/ATG5-ATG7 signaling axes. Our findings suggest that MKRN3-AS1 may be a potential prognostic biomarker and therapeutic target for HCC.
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BibTeX
@article{wang2026lncrna,
title = {{LncRNA MKRN3-AS1 promotes metastasis and autophagy of hepatocellular carcinoma by sponging multiple microRNAs}},
author = {Fei Wang and Jizhe Liu and Gaoxiong Wang and Dong Liang and Yindan Zhang and Liping Yang and Xiaoyuan Zheng and Niangmei Cheng and Yang Zhou and Yingchao Wang and Jingfeng Liu and Bixing Zhao},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-62640-x},
url = {https://doi.org/10.1038/s41598-026-62640-x},
note = {CC BY},
}
RIS
TY - JOUR
TI - LncRNA MKRN3-AS1 promotes metastasis and autophagy of hepatocellular carcinoma by sponging multiple microRNAs
AU - Fei Wang
AU - Jizhe Liu
AU - Gaoxiong Wang
AU - Dong Liang
AU - Yindan Zhang
AU - Liping Yang
AU - Xiaoyuan Zheng
AU - Niangmei Cheng
AU - Yang Zhou
AU - Yingchao Wang
AU - Jingfeng Liu
AU - Bixing Zhao
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-62640-x
UR - https://doi.org/10.1038/s41598-026-62640-x
AB - Hepatocellular carcinoma is one of the most common malignant tumors with poor clinical outcomes. Increasing numbers of long noncoding RNAs have been shown to be involved in the carcinogenesis and progression of HCC. However, the expressions, clinical significances, and roles of most lncRNAs in HCC are still unknown. In clinical samples, we utilized qPCR assays to measure the expression level of lncRNA MKRN3-AS1 in hepatocellular carcinoma (HCC) tissues compared with normal/adjacent tissues and analyzed its correlation with patient prognosis. Gain-of-function and loss-of-function experiments were performed in HCC cells to examine the effects of lncRNA MKRN3-AS1 on cell migration, invasion, and autophagy. For mechanistic investigation, bioinformatics analysis and molecular biology experiments were employed to verify the role of MKRN3-AS1 as a competitive endogenous RNA. Additionally, a mouse metastatic tumor model was established via tail vein injection to observe the impact of MKRN3-AS1 on lung metastasis of hepatocellular carcinoma. We found that lncRNA MKRN3-AS1 was dramatically upregulated in HCC tissues and associated with poor prognosis. Functionally, lncRNA MKRN3-AS1 promoted migration, invasion and autophagy of HCC cells. Mechanistically, MKRN3-AS1 acted as a “molecular sponge” for multiple miRNAs. By targeting miR-601, MKRN3-AS1 upregulate the expression of ZEB1, which directly promoted the invasion and migration of HCC cells. In addition, MKRN3-AS1 promoted autophagy via the miR-4487/ULK1 and miR-6881-3p/ATG5-ATG7 axes, which may enhance the stemness of HCC cells and thereby indirectly facilitate tumor invasion and migration. In mouse model, over-expression of MKRN3-AS1 facilitated lung metastasis of HCC. Collectively, The oncogenic function of MKRN3-AS1 in hepatocellular carcinoma may be attributed to its regulation of the miR-601/ZEB1, miR-4487/ULK1, and miR-6881-3p/ATG5-ATG7 signaling axes. Our findings suggest that MKRN3-AS1 may be a potential prognostic biomarker and therapeutic target for HCC.
SN - 2045-2322
ER -