miR-326 inhibits the progression of papillary thyroid carcinoma by targeting MAPK1 and ERBB4

Nie, Furong; Li, Q X; Wei, Hongfa; Ma, Yaqi

doi:10.4149/neo_2020_190731n696

Cited by 16 publications

(16 citation statements)

References 24 publications

(24 reference statements)

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“…Some miRNAs are also involved in immune regulation [ 36 , 37 ]. MiR-326 is involved in the progress of various tumors, including lung cancer, and acts as an inhibitory factor [ 21 , 38 , 39 ]. However, the regulatory effect of miR-326 on immune checkpoint has been rarely explored.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-326 attenuates immune escape and prevents metastasis in lung adenocarcinoma by targeting PD-L1 and B7-H3

Shao

Wang

et al. 2021

Cell Death Discov.

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Tumor-infiltrating T cells are highly expressive of inhibitory receptor/immune checkpoint molecules that bind to ligand expressed by tumor cells and antigen-presenting cells, and eventually lead to T cell dysfunction. It is a hot topic to restore T cell function by targeting immune checkpoint. In recent years, immunotherapy of blocking immune checkpoint and its receptor, such as PD-L1/PD-1 targeted therapy, has made effective progress, which brings hope for patients with advanced malignant tumor. However, only a few patients benefit from directly targeting these checkpoints or their receptors by small compounds or antibodies. Since the complexity of the regulation of immune checkpoints in tumor cells, further research is needed to identify the novel endogenous regulators of immune checkpoints which can help for developing effective drug target to improve the effect of immunotherapy. Here, we verified that microRNA-326 (miR-326) repressed the gene expression of immune checkpoint molecules PD-L1 and B7-H3 in lung adenocarcinoma (LUAD). We detected that the expression of miR-326 in LUAD tissue was negatively correlated with PD-L1/B7-H3. The repression of PD-L1 and B7-H3 expression through miR-326 overexpression leads to the modification the cytokine profile of CD8+ T cells and decreased migration capability of tumor cells. Meanwhile, the downregulation of miR-326 promoted tumor cell migration. Moreover, blocking PD-L1 and B7-H3 attenuated the tumor-promoting effect induced by miR-326 inhibitor. In tumor-bearing mice, the infiltration of CD8+ T cells was significantly increased and the expression of TNF-α, and IFN-γ was significantly enhanced which contributed to tumor progression after miR-326 overexpression. Collectively, miR-326 restrained tumor progression by downregulating PD-L1 and B7-H3 expression and increasing T cell cytotoxic function in LUAD. Our findings revealed a novel perspective on the complex regulation of immune checkpoint molecules. A new strategy of using miR-326 in tumor immunotherapy is proposed.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-326 attenuates immune escape and prevents metastasis in lung adenocarcinoma by targeting PD-L1 and B7-H3

Shao

Wang

et al. 2021

Cell Death Discov.

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“…12 MiR-326 has been revealed to take part in embryonic development, oncogenesis, chemotherapy resistance, immunomodulation, and cell invasion. 13 MiR-326 has also been identified as a tumor suppressor in a range of tumors, such as papillary thyroid cancer 14 and oral squamous cell cancer, 15 as well as being associated with BC development. However, the mechanism by which miR-326 modulates the advancement of BC has so far not been clearly explained.…”

Section: Introductionmentioning

confidence: 99%

Hsa_circRNA_0000518 facilitates breast cancer development via regulation of the miR‐326/FGFR1 axis

et al. 2020

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Background Breast cancer (BC) is a heterogeneous malignant tumor that threatens the health of women worldwide. Hsa_circRNA_0000518 (circ_0000518) has been revealed to be upregulated in BC tissues. However, the role and mechanism of circ_0000518 in BC are indistinct. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was implemented to detect the levels of circ_0000518, microRNA (miR)‐326, and fibroblast growth factor receptor 1 (FGFR1) mRNA in BC tissues and cells. Cell counting kit‐8 (CCK‐8), colony formation, flow cytometry, and transwell assays were executed to estimate BC cell proliferation, cell cycle progression, apoptosis, migration, and invasion. The relationship between circ_0000518 or FGFR1 and miR‐326 was verified by dual‐luciferase reporter and/or RNA immunoprecipitation (RIP) assays. The role of circ_0000518 in vivo was confirmed by xenograft assay. Results Circ_0000518 and FGFR1 were upregulated while miR‐326 was downregulated in BC tissues and cells. Circ_0000518 silencing impeded tumor growth in vivo and induced cell cycle arrest, apoptosis, cured proliferation, colony formation, migration, and invasion of BC cells in vitro. Circ_0000518 regulated FGFR1 expression via competitively binding to miR‐326 in BC cells. MiR‐326 inhibitor reversed the inhibitory influence of circ_0000518 knockdown on the malignant behaviors of BC cells. FGFR1 overexpression abolished miR‐326 mimic‐mediated influence on the malignant behaviors of BC cells. Conclusions Circ_0000518 facilitated BC development via regulation of the miR‐326/FGFR1 axis, suggesting that circ_0000518 might be a promising target for BC treatment.

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“…miR-193a-5p directly targets SPOCK1 in hepatocellular carcinoma to repress its malignancy (39). Additionally, miR-330-5p and miR-326 have both been demonstrated to play tumor-suppressive roles in PTC progression (20,21). However, research on miR-193a-5p in PTC is limited.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study showed that miR-330-5p mediates the positive regulation of long intergenic non-protein-coding RNA 003311 on cancer stem-like features in PTC (20). miR-326 suppresses PTC cell proliferation and metastasis by inhibiting MAPK1 and erb-b2 receptor tyrosine kinase (ERBB) 4 (21).…”

Section: Introductionmentioning

confidence: 99%

Circular RNA hsa_circ_0001666 sponges miR‑330‑5p, miR‑193a‑5p and miR‑326, and promotes papillary thyroid carcinoma progression via upregulation of ETV4

Zhang

Wang

et al. 2021

Oncol Rep

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Circular RNAs (circRNAs) are a group of regulators that affect the aggressive behaviors of several types of cancer. Hsa_circ_0001666 (also referred to as hsa_circ_000742) is a newly discovered circRNA that is upregulated in human papillary thyroid carcinoma (PTC) based on microarray analysis. However, the role of hsa_circ_0001666 in PTC progression remains unknown. Thus, the aim of the present study was to determine the potential function and underlying mechanism of hsa_circ_0001666 in PTC. The results demonstrated that hsa_circ_0001666 was upregulated in both PTC clinical samples and cell lines. Its expression was associated with lymph node metastasis of patients with PTC. Knocking down hsa_circ_0001666 expression inhibited cell proliferation, as evidenced by decreased cell viability, arrest of cell cycle progression at the G 1 phase and an increase in cell cycle-associated proteins. Apoptosis rates and expression levels of pro-apoptotic proteins were also increased by silencing hsa_circ_0001666. In xenograft experiments, the oncogenic effect of hsa_circ_0001666 on tumor growth was verified. Additionally, luciferase reporter assays showed that hsa_circ_0001666 and ETS variant transcription factor 4 (ETV4) shared common binding sites with three microRNAs [(miRNA/miR)-330-5p, miR-193a-5p and miR-326]. Knockdown of these miRNAs separately reversed the inhibitory effect of hsa_circ_0001666 small interfering RNAs on PTC tumor aggressiveness, and ETV4 overexpression also induced a similar effect to that of miRNA inhibitors. Thus, hsa_circ_0001666 may function as an oncogene, promoting PTC tumorigenesis via the miR-330-5p/miR-193a-5p/miR-326/ETV4 pathway. This provides a basis for identifying potential novel therapeutic targets for PTC.

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miR-326 inhibits the progression of papillary thyroid carcinoma by targeting MAPK1 and ERBB4

Cited by 16 publications

References 24 publications

MicroRNA-326 attenuates immune escape and prevents metastasis in lung adenocarcinoma by targeting PD-L1 and B7-H3

MicroRNA-326 attenuates immune escape and prevents metastasis in lung adenocarcinoma by targeting PD-L1 and B7-H3

Hsa_circRNA_0000518 facilitates breast cancer development via regulation of the miR‐326/FGFR1 axis

Circular RNA hsa_circ_0001666 sponges miR‑330‑5p, miR‑193a‑5p and miR‑326, and promotes papillary thyroid carcinoma progression via upregulation of ETV4

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