The New Role of HNF1A-NAS1/miR-214/INHBA Signaling Axis in Colorectal Cancer

Xuan Zhang; Tao Wu; Rujia Qin; Xinyi Cai; Yongchun Zhou; Xiaoxiong Wang; Zhongjun Shang; Guoyu Li; Renfang Yang; Chao Dong; Jinsha Li; Yongping Ren; Rong Ding; Yunfeng Li

doi:10.31083/j.fbl2811301

Frontiers in Bioscience-Landmark (Nov 2023)

The New Role of HNF1A-NAS1/miR-214/INHBA Signaling Axis in Colorectal Cancer

Xuan Zhang,
Tao Wu,
Rujia Qin,
Xinyi Cai,
Yongchun Zhou,
Xiaoxiong Wang,
Zhongjun Shang,
Guoyu Li,
Renfang Yang,
Chao Dong,
Jinsha Li,
Yongping Ren,
Rong Ding,
Yunfeng Li

Affiliations

Xuan Zhang: Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Tao Wu: Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Rujia Qin: Department of Head and Neck Tumor Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Xinyi Cai: Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Yongchun Zhou: Laboratory of Molecular Diagnosis Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Xiaoxiong Wang: Laboratory of Molecular Diagnosis Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Zhongjun Shang: Department of Hospital Affairs, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Guoyu Li: Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Renfang Yang: Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Chao Dong: Department of Oncology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Jinsha Li: Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Yongping Ren: Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Rong Ding: Department of Minimally Invasive Intervention, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China
Yunfeng Li: Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, 650118 Kunming, Yunnan, China

DOI: https://doi.org/10.31083/j.fbl2811301
Journal volume & issue: Vol. 28, no. 11
p. 301

Abstract

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Background: Colorectal cancer (CRC) is the third most common cancer and one of the leading causes of death worldwide. Seriously threatens human life and health. Previous studies have identified that inhibin βA (INHBA) could induce tumorgenesis and progression of CRC through the regulation of the TGF-β/Smad signal axis. The abnormal expression of INHBA is related to the poor prognosis of patients. The aim of this study was to identify the molecular mechanism of HNF1A-AS1 and miR-214 regulating INHBA and carcinogenesis through bioinformatics combined with experiments. Methods: The expression of HNF1A-AS1, miRNA-214-5p, INHBA in pan-cancer and CRC were investigated in the Cancer Genome Atlas (TCGA). The correlation between HNF1A-AS1 and immune-related genes or miRNAs was explored via the Gene Expression Profiling Interactive Analysis (GEPIA) and volcano plots, respectively. The association between HNF1A-AS1 and differentially expressed miRNAs was constructed by TargetScan. The miRDB, miRWalk, and TargetScan databases were utilized to predict the target genes of hsa-miR-214. The expression of INHBA in tissues and cell lines of CRC was examined by RT-qPCR and western blot assay. Results: The INHBA and HNF1A-AS1 expressions were increased in Colon adenocarcinoma (COAD) and Rectum adenocarcinoma (READ) of the TCGA database. Hsa-miR-214 was relatively less expressed in CRC tissues compared with para-cancer tissues. The expression of HNF1A-AS1 was negatively correlated with hsa-miR-214. INHBA was one of the target genes of hsa-miR-214 based on miRDB, miRWalk, and TargetScan databases. The specific binding sites of INHBA-3’UTR and miR-214-5p were identified by starBase. The expression level of INHBA was positively correlated with the T stage of tumor and negatively correlated with overall survival (OS) and disease-free survival (DFS) in CRC patients. The results of RT-qPCR and western blot indicated that the expression of INHBA in tissues and cell lines in CRC was higher than those in para-carcinoma tissues and normal colon cell lines, respectively. Conclusions: These findings suggested that HNF1A-AS1 and miRNA-214-5p were key upstream non-coding RNAs of INHBA. The HNF1A-AS1/miR-214/INHBA signal axis plays a significant role in the tumorgenesis and progression of CRC. By interfering with HNF1A-AS1 and INHBA genes on HT29 and SW480 cells, it was found that HNF1A-AS1 and INHBA genes may be important target genes in CRC.

Published in Frontiers in Bioscience-Landmark

ISSN: 2768-6701 (Print); 2768-6698 (Online)
Publisher: IMR Press
Country of publisher: Singapore
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General)
Website: https://www.imrpress.com/journal/FBL

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