CircPDZD8 promotes gastric cancer progression by regulating CHD9 via sponging miR-197-5p

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Abstract

CircRNAs have been shown to be associated with gastric cancer tumorigenesis. But little was known about the role of circPDZD8 in gastric cancer. CircPDZD8 was up-regulated in gastric cancer tissues and cells, Kaplan-Meier survival analysis indicated that gastric patients had a poor overall survival when circPDZD8 levels were high. CircPDZD8 knockdown could hinder proliferation and migration of gastric cancer cells. MiR-197-5p, which was down-regulated in gastric cancer, was shown to be a target of circPDZD8 and was inversely correlated with circPDZD8 expression. CHD9, as a target gene of miR-197-5p, was negatively regulated by miR-197-5p and positively correlated with circPDZD8 expression. Importantly, circPDZD8 could up-regulate CHD9 expression by sponging miR-197-5p, and modulate cell progression by regulation of the miR-197-5p/CHD9 axis in gastric cancer. CircPDZD8 knockdown repressed the progression of gastric cancer cells by sponging miR-197-5p and down-regulating CHD9.

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Most cited references 36

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The multilayered complexity of ceRNA crosstalk and competition.

Yvonne Tay, John Rinn, Pier Paolo Pandolfi (2014)

Recent reports have described an intricate interplay among diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs. These RNA transcripts act as competing endogenous RNAs (ceRNAs) or natural microRNA sponges - they communicate with and co-regulate each other by competing for binding to shared microRNAs, a family of small non-coding RNAs that are important post-transcriptional regulators of gene expression. Understanding this novel RNA crosstalk will lead to significant insight into gene regulatory networks and have implications in human development and disease.

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Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA

Min Wang, Chao Mao, Lianlian Ouyang … (2019)

The regulatory loop between long noncoding RNAs (lncRNAs) and microRNAs has a dynamic role in transcriptional and translational regulation, and is involved in cancer. However, the regulatory circuitry between lncRNAs and microRNAs in tumorigenesis remains elusive. Here we demonstrate that a nuclear lncRNA LINC00336 is upregulated in lung cancer and functions as an oncogene by acting as a competing endogenous RNA (ceRNAs). LINC00336 bound RNA-binding protein ELAVL1 (ELAV-like RNA-binding protein 1) using nucleotides 1901–2107 of LINC00336 and the RRM interaction domain and key amino acids (aa) of ELAVL1 (aa 101–213), inhibiting ferroptosis. Moreover, ELAVL1 increased LINC00336 expression by stabilizing its posttranscriptional level, whereas LSH (lymphoid-specific helicase) increased ELAVL1 expression through the p53 signaling pathway, further supporting the hypothesis that LSH promotes LINC00336 expression. Interestingly, LINC00336 served as an endogenous sponge of microRNA 6852 (MIR6852) to regulate the expression of cystathionine-β-synthase (CBS), a surrogate marker of ferroptosis. Finally, we found that MIR6852 inhibited cell growth by promoting ferroptosis. These data show that the network of lncRNA and ceRNA has an important role in tumorigenesis and ferroptosis.

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Noncoding RNAs in gastric cancer: implications for drug resistance

Ling Wei, Jujie Sun, Nasha Zhang … (2020)

Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. Advanced gastric cancer patients can notably benefit from chemotherapy including adriamycin, platinum drugs, 5-fluorouracil, vincristine, and paclitaxel as well as targeted therapy drugs. Nevertheless, primary drug resistance or acquisition drug resistance eventually lead to treatment failure and poor outcomes of the gastric cancer patients. The detailed mechanisms involved in gastric cancer drug resistance have been revealed. Interestingly, different noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are critically involved in gastric cancer development. Multiple lines of evidences demonstrated that ncRNAs play a vital role in gastric cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically summarized the emerging role and detailed molecular mechanisms of ncRNAs impact drug resistance of gastric cancer. Additionally, we propose the potential clinical implications of ncRNAs as novel therapeutic targets and prognostic biomarkers for gastric cancer.

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Author and article information

Journal

Journal ID (nlm-ta): Aging (Albany NY)

Journal ID (publisher-id): Aging

Title: Aging (Albany NY)

Publisher: Impact Journals

ISSN (Electronic): 1945-4589

Publication date Collection: 15 October 2020

Publication date (Electronic): 13 October 2020

Volume: 12

Issue: 19

Pages: 19352-19364

Affiliations

[1 ]Department of General Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian 223300, Huaiyin, Jiangsu Province, China

[2 ]Department of Gastroenterology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaiyin 223300, Huaian, Jiangsu Province, China

Author notes

Correspondence to: Tianfang Xia; email: jsxiatianfang@163.com; https://orcid.org/0000-0001-9533-3913

Article

Publisher ID: 103805 Publisher ID: 103805

DOI: 10.18632/aging.103805

PMC ID: 7732272

PubMed ID: 33049714

SO-VID: 5e2b60d8-1721-450b-a8ee-785a4dfde3a0

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

CircPDZD8 promotes gastric cancer progression by regulating CHD9 via sponging miR-197-5p

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Karger: Oncology

Most cited references 36

The multilayered complexity of ceRNA crosstalk and competition.

Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA

Noncoding RNAs in gastric cancer: implications for drug resistance

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