Dataset Information

M⁶A Modification of Long Non-Coding RNA HNF1A-AS1 Facilitates Cell Cycle Progression in Colorectal Cancer via IGF2BP2-Mediated CCND1 mRNA Stabilization.

ABSTRACT:

Background

Long non-coding RNAs modulate tumor occurrence through different molecular mechanisms. It had been reported that HNF1A-AS1 (HNF1A Antisense RNA 1) was differently expressed in multiple tumors. The role of HNF1A-AS1 in colorectal cancer was less analyzed, and the mechanism of regulating the cell cycle has not been completely elucidated.

Methods

Differentially expressed lncRNAs were screened out from the TCGA database. HNF1A-AS1 was examined in CRC clinical samples and cell lines by RT-qPCR. CCK8 assay, colony formation assay, flow cytometry, transwell assays, tube forming assay and vivo experiments were performed to study the function of HNF1A-AS1 in CRC tumor progression. Bioinformatic analysis, luciferase report assay, RNA pull-down and RIP assays were carried out to explore proteins binding HNF1A-AS1 and the potential downstream targets.

Results

Our results showed that HNF1A-AS1 was upregulated in CRC and associated with unfavorable prognosis. HNF1A-AS1 promoted proliferation, migration and angiogenesis, accelerated cell cycle and reduced cell apoptosis in CRC. Bioinformatics prediction and further experiments proved that HNF1A-AS1 could promote CCND1 expression by suppressing PDCD4 or competitively sponging miR-93-5p. Meanwhile, METTL3 mediated HNF1A-AS1 m⁶A modification and affected its RNA stability. HNF1A-AS1/IGF2BP2/CCND1 may act as a complex to regulate the stability of CCND1.

Conclusion

In summary, our result reveals the novel mechanism in which m⁶A-mediated HNF1A-AS1/IGF2BP2/CCND1 axis promotes CRC cell cycle progression, along with competitively sponging miR-93-5p to upregulate CCND1, demonstrating its significant role in cell cycle regulation and suggesting that HNF1A-AS1 may act as a potential prognostic marker of colorectal cancer in the future.

SUBMITTER: Bian Y

PROVIDER: S-EPMC9562639 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

m<sup>6</sup>A Modification of Long Non-Coding RNA HNF1A-AS1 Facilitates Cell Cycle Progression in Colorectal Cancer via IGF2BP2-Mediated CCND1 mRNA Stabilization.

Bian Yibo Y Wang Yang Y Xu Shufen S Gao Zhishuang Z Li Chao C Fan Zongyao Z Ding Jie J Wang Keming K

Cells 20220927 19

<h4>Background</h4>Long non-coding RNAs modulate tumor occurrence through different molecular mechanisms. It had been reported that HNF1A-AS1 (HNF1A Antisense RNA 1) was differently expressed in multiple tumors. The role of HNF1A-AS1 in colorectal cancer was less analyzed, and the mechanism of regulating the cell cycle has not been completely elucidated.<h4>Methods</h4>Differentially expressed lncRNAs were screened out from the TCGA database. HNF1A-AS1 was examined in CRC clinical samples and ce ...[more]

PMID: 36230970

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Project description:VIM‑AS1, a cancer‑specific long non‑coding RNA, has been recognized as a pivotal regulator in multiple types of cancer. However, the role of VIM‑AS1 in the proliferation and resistance to anti‑androgen therapy of LNCaP and C4‑2 prostate cancer cells remains to be determined. In the current study, gain‑and‑loss experiments were used to investigate the effects of VIM‑AS on the proliferation and anti‑androgen therapy of LNCaP and C4‑2 cells. RNA sequencing, RNA pulldown and RNA immunoprecipitation were used to elucidate the underlying mechanism of VIM‑AS1 driving prostate progression. It was demonstrated that VIM‑AS1 was upregulated in C4‑2 cells, an established castration‑resistant prostate cancer (CRPC) cell line, compared with in LNCaP cells, an established hormone‑sensitive prostate cancer cell line. The present study further demonstrated that VIM‑AS1 was positively associated with the clinical stage of prostate cancer. Functionally, overexpression of VIM‑AS1 decreased the sensitivity to enzalutamide treatment and enhanced the proliferation of LNCaP cells in vitro, whereas knockdown of VIM‑AS1 increased the sensitivity to enzalutamide treatment and reduced the proliferation of C4‑2 cells in vitro and in vivo. Mechanistically, 3‑hydroxy‑3‑methylglutaryl‑CoA synthase 1 (HMGCS1) was identified as one of the direct downstream targets of VIM‑AS1, and VIM‑AS1 promoted HMGCS1 expression by enhancing HMGCS1 mRNA stability through a VIM‑AS1/insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2)/HMGCS1 RNA‑protein complex. Rescue assays indicated that knockdown of HMGCS1 expression ameliorated the increase in proliferation and enzalutamide resistance of prostate cancer cells induced by VIM‑AS1 overexpression. Overall, the present study determined the roles and mechanism of the VIM‑AS1/IGF2BP2/HMGCS1 axis in regulating proliferation and enzalutamide sensitivity of prostate cancer cells and suggested that VIM‑AS1 may serve as a novel therapeutic target for the treatment of patients with CRPC.

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Dataset Information

M⁶A Modification of Long Non-Coding RNA HNF1A-AS1 Facilitates Cell Cycle Progression in Colorectal Cancer via IGF2BP2-Mediated CCND1 mRNA Stabilization.

Background

Methods

Results

Conclusion

Publications

m<sup>6</sup>A Modification of Long Non-Coding RNA HNF1A-AS1 Facilitates Cell Cycle Progression in Colorectal Cancer via IGF2BP2-Mediated CCND1 mRNA Stabilization.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

M6A Modification of Long Non-Coding RNA HNF1A-AS1 Facilitates Cell Cycle Progression in Colorectal Cancer via IGF2BP2-Mediated CCND1 mRNA Stabilization.

Background

Methods

Results

Conclusion

Publications

m<sup>6</sup>A Modification of Long Non-Coding RNA HNF1A-AS1 Facilitates Cell Cycle Progression in Colorectal Cancer via IGF2BP2-Mediated CCND1 mRNA Stabilization.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

M⁶A Modification of Long Non-Coding RNA HNF1A-AS1 Facilitates Cell Cycle Progression in Colorectal Cancer via IGF2BP2-Mediated CCND1 mRNA Stabilization.