miR-636 inhibits EMT, cell proliferation and cell cycle of ovarian cancer by directly targeting transcription factor Gli2 involved in Hedgehog pathway

Ma, Jiong; Zhou, Chunxia; Chen, Xuejun

doi:10.21203/rs.3.rs-52894/v2

Cited by 3 publications

(3 citation statements)

References 39 publications

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“…26 Next, we searched the potential targets of circ_0010235 and validated that miR-636 was directly targeted by circ_0010235. MiR-636 plays a tumor-promoting or tumor-suppressing role in different cancer, acting as a tumor inhibitor in cervical cancer and ovarian cancer 27,28 and a promoter in bladder cancer. 29 In lung cancer, interference of circ_100876 suppressed lung cancer progression via regulating miR-636/ RET axis.…”

Section: Discussionmentioning

confidence: 99%

Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis

Jixing

Huang

et al. 2022

Thoracic Cancer

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Background: Circular RNAs (circRNAs) are a class of important regulators in various human cancers, including lung cancer. Here, we aimed to investigate the role of circ_0010235 in lung cancer. Methods: The expression of circ_0010235, microRNA-636 (miR-636) and PDL1 was measured by quantitative real-time PCR (qRT-PCR). Cell proliferation was evaluated by CCK-8, colony formation, and 5-ethynyl-2 0 -deoxyuridine (EdU) assays. Cell apoptosis was detected by flow cytometry. Cell invasion was assessed by transwell assay. All protein levels were determined by western blot assay. In order to detect the roles of circ_0010235 in immune escape, lung cancer cells were cocultured with peripheral blood mononuclear cells (PBMCs) or cytokine-induced killer (CIK) cells in vitro. The relationship between miR-636 and circ_0010235 or PDL1 was verified by dual-luciferase reporter assay and RNA pulldown assay. Immunohistochemistry (IHC) analysis was used to detect Ki67 and programmed death-ligand 1 (PDL1) expression. A xenograft tumor model was established to verify the function of circ_0010235 in vivo. Results: Circ_0010235 was overexpressed in lung cancer. Circ_0010235 knockdown inhibited proliferation, invasion and immune escape and promoted apoptosis of lung cancer cells. MiR-636 was a target of circ_0010235, and miR-636 inhibition reversed the effects of circ_0010235 knockdown in lung cancer cells. PDL1 was a direct target of miR-636, and miR-636 suppressed the proliferation and invasion and increased apoptosis and antitumor immunity in lung cancer cells by downregulating PDL1. Moreover, circ_0010235 positively regulated PDL1 expression by sponging miR-636. Additionally, circ_0010235 knockdown hampered tumorigenesis in vivo. Conclusion: Circ_0010235 knockdown inhibited lung cancer progression and increased antitumor immunity by regulating the miR-636/PDL1 axis.

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Section: Discussionmentioning

confidence: 99%

Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis

Jixing

Huang

et al. 2022

Thoracic Cancer

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“…Another example is bta-miR-26a which also reduced the abundance of PCK1 [44,45]. Moreover, the oncosuppressor miR-20a-3p was identified in melanoma, tongue squamous cell carcinoma, and hepatocellular carcinoma, and the oncosuppressor miR-636 was also identified in lung cancer, nasopharyngeal carcinoma, cervical cancer, endometrial cancer, ovarian cancer, and hepatocellular carcinoma [46][47][48][49][50][51][52][53][54][55][56]. It was reported that high miR-20a-3p and miR-636 expression were correlated with poor OS of CRC patients and this was consistent with our results.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel miRNAs, Targeting Genes, Signaling Pathway, and the Small Molecule for Overcoming Oxaliplatin Resistance of Metastatic Colorectal Cancer

Misbah

Kumar

Shen

2022

BioMed Research International

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One of the globally common cancers is colorectal cancer (CRC). At present, a surgical approach remains a good option for CRC patients; however, 20% of surgically treated CRC patients experience metastasis. Currently, even the first-line used drug, oxaliplatin, remains inadequate for treating metastatic CRC, and its side effect of neurotoxicity is a major problem when treating CRC. The Gene Omnibus GSE42387 database contains gene expression profiles of parental and oxaliplatin-resistant LoVo cell lines. Differentially expressed genes (DEGs) between parental and oxaliplatin-resistance LoVo cells, protein-protein interactions (PPIs), and a pathway analysis were determined to identify overall biological changes by an online DAVID bioinformatics analysis. The ability of DEGs to predict overall survival (OS) and disease-free survival (DFS) was validated by the SPSS 22.0, using liver metastasis CRC patient samples of GSE41258. The bioinformatics web tools of the GEPIA, the Human Protein Atlas, WebGestalt, and TIMER platforms were used. In total, 218 DEGs were identified, among which 105 were downregulated and 113 were upregulated. After mapping the PPI networks and pathways, 60 DEGs were identified as hub genes (with high degrees). Six genes (TGFB1, CD36, THBS1, FABP1, PCK1, and IRS1) were involved with malaria, PPAR signaling, and the adipocytokine signaling pathway. High expressions of CD36 and PCK1 were associated with the poor survival of CRC patients in the GSE41258 database. We predicted specific micro (mi)RNAs that targeted the 3 ′ untranslated region (UTR) of PCK1 by using miRWalk. It was found that three miRNAs, viz., miR-7-5p, miR-20a-3p, and miR-636, may be upstream targets of those genes. High expression levels of miR-7-5p, miR-20a-3p, and miR-636 were associated with poor OS of CRC patients, and the small-molecule compound, mersalyl, is a promising drug for treating oxaliplatin-resistant CRC. In conclusion, miR-7-5p miR-20a-3p, and miR-636 targeted the PCK1 biomarker in the PPAR signaling pathway, which is involved in oxaliplatin-resistant CRC. Meanwhile, mersalyl was identified as a potential drug for overcoming oxaliplatin resistance in CRC. Our findings may provide novel directions and strategies for CRC therapies.

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“…Thus, circPTPRA can play opposite roles in different tumors, which may be related to tumor heterogeneity. Studies have reported that miR-636 acts as a tumor suppressor [30] or oncogene [29] in other tumors, but its role in PDAC is unclear. IGF2BP1 promotes PDAC cell proliferation by activating AKT, which can be used as a driver and a therapeutic target in PDAC [31].…”

Section: Discussionmentioning

confidence: 99%

CircPTPRA promotes the progression of pancreatic ductal adenocarcinoma via the miR-140-5p/LMNB1 axis

Wang

Xiang

et al. 2022

Preprint

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Background Growing evidence suggests that circular RNAs (circRNAs) are important factors in cancer progression. Nevertheless, the role of circRNAs in the progression of pancreatic ductal adenocarcinoma (PDAC) remains unclear. Methods CircPTPRA was identified based on our previous circRNA array data analysis. Wound healing, transwell and EdU assays were performed to investigate the effect of circPTPRA on the migration, invasion and proliferation of PDAC cells in vitro. RNA pull-down, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were conducted to verify the binding of circPTPRA with miR-140-5p. Subcutaneous xenograft models were constructed for in vivo experiments. Results CircPTPRA was significantly upregulated in PDAC tissues and cells compared to normal controls. Moreover, circPTPRA overexpression was positively correlated with lymph node invasion and worse prognosis in PDAC patients. In addition, overexpression of circPTPRA promoted PDAC migration, invasion, proliferation and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, circPTPRA upregulates LaminB1 (LMNB1) expression by sponging miR-140-5p and ultimately promots the progression of PDAC. Conclusions This study revealed that circPTPRA plays an important role in the progression of PDAC by sponging miR-140-5p. It can be explored as a potential prognostic marker and therapeutic target for PDAC.

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miR-636 inhibits EMT, cell proliferation and cell cycle of ovarian cancer by directly targeting transcription factor Gli2 involved in Hedgehog pathway

Cited by 3 publications

References 39 publications

Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis

Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis

Identification of Novel miRNAs, Targeting Genes, Signaling Pathway, and the Small Molecule for Overcoming Oxaliplatin Resistance of Metastatic Colorectal Cancer

CircPTPRA promotes the progression of pancreatic ductal adenocarcinoma via the miR-140-5p/LMNB1 axis

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