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LncRNA RP11-93B14.5 promotes gastric cancer cell growth through PI3K/AKT signaling pathway

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Abstract

Objective: Emerging evidence indicates that long non-coding RNA (lncRNA) RP11-93B14.5 facilitates tumor progression in variety of malignancies. The present study proposed to study the functional effect of lncRNA RP11-93B14.5 in gastric cancer (GC) as well as the underlying mechanism. Methods: Bioinformatics analysis was utilized to analyze lncRNA expression in GC tissues. siRNA was used for knockdown of RP11-93B14.5 in GC cells MKN45 and KATO III. The stable knockdown cell lines were constructed by CRISPR-Cas9. Cell counting kit-8 (CCK-8) assay and soft agar colony formation assay were used to analyze GC cell viability. Flow cytometry analysis was performed to analyze the cell cycle distribution of MKN45 and KATO III. RNA sequencing (RNA-seq) was employed to detect differential genes after transfection with siRP11-93B14.5. Quantitative PCR (Q-PCR) was used to examine gene expression in GC cell lines. Western-blot assay was used to measure protein levels. RNA fluorescent in situ hybridization (FISH) was conducted for lncRNA cellular location and expression. Results: Based on the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database, RP11-93B14.5 was upregulated in GC tissue, which was also verified in GC cell lines in comparison to the normal gastric epithelial HFE145 cells. Knockdown of RP11-93B14.5 decreased cell viability and the colony number of MKN45 and KATO III cells, and altered cell cycle distribution in vitro. RNA-seq analysis revealed RP11-93B14.5 may modulate genes expression of S100A2 and TIMP2 in MKN45 and KATO III cells. Mechanistically, RP11-93B14.5 may drive the progression of GC via S100A2 related-PI3K/AKT signaling pathway. Conclusions: LncRNA RP11-93B14.5 knockdown alleviated the malignant phenotypes of GC cells through regulating PI3K/AKT. Our results provide evidence for the role of lncRNAs in regulating tumor progression.

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Data Availability

The data used to support the findings of the present study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81803237), the grant from Natural Science Foundation of Sichuan Province, China (No. 2023NSFSC1848), the grant from Natural Science Foundation of Anhui Provincial Education Department (No. KJ2019A0421) and the grant from Science and Technology Program of Luzhou, China (No. 2022-JYJ-113).

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Author notes

  1. Qianxiu Li and Zhongxiu Zhu contributed equally.

Authors and Affiliations

  1. Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, China

    Qianxiu Li, Xu Wu, Huan Yang, Xiaobing Li, Wanping Li, Yueshui Zhao, Fukuan Du, Yu Chen, Jing Shen, Zhangang Xiao, Meijuan Chen, Fang Wang, Li Gu, Yuhong Sun & Mingxing Li

  2. Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, 646000, Sichuan, China

    Qianxiu Li, Xu Wu, Huan Yang, Xiaobing Li, Wanping Li, Yueshui Zhao, Fukuan Du, Yu Chen, Jing Shen, Zhangang Xiao, Meijuan Chen, Fang Wang, Li Gu, Yuhong Sun & Mingxing Li

  3. The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), Jinan, 250000, Shandong, China

    Zhongxiu Zhu

  4. Nanchong Key Laboratory of Individualized Drug Therapy, Department of Pharmacy, The Second Clinical Medical College, Nanchong Central Hospital, North Sichuan Medical College, Nanchong, 637000, Sichuan, China

    Hanyu Zhang

  5. South Sichuan Institute of Translational Medicine, Luzhou, 646000, Sichuan, China

    Xu Wu, Yueshui Zhao, Fukuan Du, Yu Chen, Jing Shen, Zhangang Xiao & Mingxing Li

  6. Antibiotics Research and Re-evaluation Key Laboratory of Sichuan, School of Pharmacy, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu, 610106, Sichuan, China

    Lan Lu

  7. Department of Gastroenterology, The first affiliated hospital of Wannan Medical College, Wuhu, 241000, Anhui, China

    Yuliang Jia

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  1. Qianxiu Li
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Contributions

ML and YJ designed and conceived the study. XW, FD, WL, FW, LG and YS conducted the bioinformatics analysis. XW, QL, ZZ, HZ, HY, LL, MC, YZ, YC, JS and ZX performed the experiments. XW, QL, HY, XL, YZ, WL, YC, JS, ZX and LG analyzed the data. YC, JS, ZX, YS and MC provided the resources of experiments for this study. QL wrote the original draft. ML, XW, ZZ and LL reviewed and edited the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yuliang Jia or Mingxing Li.

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Supplementary Figure S1:

CRISPR-Cas9 induced knockdown of lncRNA RP11-93B14.5 suppressed GC cell proliferation through modulating PI3K/AKT pathway.

Supplementary Table S1:

Primer sequences and target sequences used in the present study.

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Li, Q., Zhu, Z., Zhang, H. et al. LncRNA RP11-93B14.5 promotes gastric cancer cell growth through PI3K/AKT signaling pathway. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00844-6

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