Journal
TRANSLATIONAL ONCOLOGY
Volume 18, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2022.101351
Keywords
Gastric cancer; Chemoresistance; HNF1A-AS1; miR-30b-5p; EIF5A2; Epithelial mesenchymal transition
Categories
Funding
- Beijing Municipal Science and Technology Commission [D171100006517002, D171100006517004]
- CAMS Innovation Fund for Medical Sciences [2020-I2M-CT-B-017]
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The current study found that HNF1A-AS1 promotes 5-FU resistance in gastric cancer (GC) by acting as a ceRNA of miR-30b-5p and promoting EIF5A2-induced epithelial mesenchymal transition (EMT) process. This indicates that HNF1A-AS1 is a potential therapeutic target for alleviating GC chemoresistance.
Background: Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide and chemoresistance is a major cause for its poor prognosis. Long non-coding RNAs (lncRNAs) are associated with cancer chemoresistance. The current study sought to explore the mechanism of lncRNA HNF1A antisense RNA 1 (HNF1A-AS1) in mediating 5-fluorouracil (5-FU) resistance of GC. Methods: qRT-PCR was performed to detect the expression level of HNF1A-AS1 in GC tissues and cells. Abnormal expression of HNF1A-AS1 in GC cells was induced by lentivirus infection. Protein levels of EIF5A2, E-Cadherin, Vimentin and N-Cadherin were detected using western blot. Competitive endogenous RNA (ceRNA) mechanisms were explored through luciferase assays and RNA immunoprecipitation (RIP) assays. Functional experiments of chemoresistance were performed by CCK-8 assays, colony formation assays and flow cytometry with the treatment of 5-FU. Mouse tumor xenograft assays were performed to verify the findings in vivo. Results: The findings showed HNF1A-AS1 was significantly upregulated in GC tissues especially in chemoresistance group. Findings from in vitro and in vivo experiments showed HNF1A-AS1 increased cell viability and proliferation, repressed apoptosis and promoted xenograft tumors growth in the presence of 5-FU. Mechanistic studies revealed HNF1A-AS1 promoted chemoresistance by facilitating epithelial mesenchymal transition (EMT) process through upregulating EIF5A2 expression and HNF1A-AS1 acted as a sponge of miR-30b-5p. Conclusions: The findings from the current study showed HNF1A-AS1 promoted 5-FU resistance by acting as a ceRNA of miR-30b-5p and promoting EIF5A2-induced EMT process in GC. This indicates that HNF1A-AS1 is a potential therapeutic target for alleviating GC chemoresistance.
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