The dual role of microRNA (miR)-20b in cancers: Friend or foe?

İlhan, Ahmet; Golestani, Shayan; Shafagh, Seyyed Ghavam; Asadi, Fatemeh; Daneshdoust, Danyal; Al-Naqeeb, Bashar Zuhair Talib; Nemati, Mohammed Mahdi; Khalatbari, Fateme; Yaseri, Amirhossein Fakhre

doi:10.1186/s12964-022-01019-7

Cited by 15 publications

(7 citation statements)

References 126 publications

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“…In addition, the PI3K/AKT/mTOR signaling pathway is closely related to autophagy. Previous reports indicate that autophagy is regulated by the PI3K/AKT/mTOR signaling pathway to regulate tumor migration, invasion, and proliferation [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

LAMC2 regulates proliferation, migration, and invasion mediated by the Pl3K/AKT/mTOR pathway in oral squamous carcinoma

Shan¹,

Liang²,

Feng³

et al. 2023

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Background Oral squamous cell carcinoma (OSCC) is a common malignant tumor. Recently, Laminin Gamma 2 (LAMC2) has been shown to be abnormally expressed in OSCC; however, how LAMC2 signaling contributes to the occurrence and development of OSCC and the role of autophagy in OSCC has not been fully explored. This study aimed to analyze the role and mechanism of LAMC2 signaling in OSCC and the involvement of autophagy in OSCC. Methods To explore the mechanism by which LAMC2 is highly expressed in OSCC, we used small interfering RNA (siRNA) to knock down LAMC2 to further observe the changes in the signaling pathway. Furthermore, we used cell proliferation assays, Transwell invasion assays, and wound-healing assays to observe the changes in OSCC proliferation, invasion, and metastasis. RFP-LC3 was used to detect the level of autophagy intensity. A cell line-derived xenograft (CDX) model was used to detect the effect of LAMC2 on tumor growth in vivo . Results This study found that the level of autophagy was correlated with the biological behavior of OSCC. The downregulation of LAMC2 activated autophagy and inhibited OSCC proliferation, invasion, and metastasis via inhibiting the PI3K/AKT/mTOR pathway. Moreover, autophagy has a dual effect on OSCC, and the synergistic downregulation of LAMC2 and autophagy can inhibit OSCC metastasis, invasion, and proliferation via the PI3K/AKT/mTOR pathway. Conclusions LAMC2 interacts with autophagy to regulate OSCC metastasis, invasion, and proliferation via the PI3K/AKT/mTOR pathway. LAMC2 down-regulation can synergistically modulate autophagy to inhibit OSCC migration, invasion, and proliferation.

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Section: Introductionmentioning

confidence: 99%

LAMC2 regulates proliferation, migration, and invasion mediated by the Pl3K/AKT/mTOR pathway in oral squamous carcinoma

Shan¹,

Liang²,

Feng³

et al. 2023

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“…[32,33] Pre-miR20b is responsible for miRNA biogenesis involved in tumor suppression; CDE2GG is recognized as a constitutive decay element (CDE) by RNA binding protein (RBP) Roquin mediating mRNA degradation for autoimmune responses. [32,34,35] We carried out RT-stop chemical probing experiments at six different concentrations of probe (1.5, 2.5, 5.0, 7.5, 10.0, and 12.5 mM SHAPE and 1%, 0.94%, 0.88%, 0.82%, and 0.78% DMS) and determined the reactivity at each concentration (Figure 1A-B). The following trends were observed: i) nucleotides in both the stem and apical loop are subject to cooperative and anti-cooperative events: A nonlinear trend in reactivity, as the concentration of probe increases, indicates a cooperative or anti-cooperative event.…”

Section: Resultsmentioning

confidence: 99%

Cooperativity in RNA chemical probing experiments modulates RNA 2D structure

Arnold,

Cohn,

Bose

et al. 2023

Preprint

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Small molecule chemical probes that covalently bond atoms of flexible nucleotides are widely employed in RNA structure determination. Atomistic molecular dynamic (MD) simulations recently revealed that the binding of RNA by chemical probes is influenced by cooperative effects, leading to measured reactivities that depend on the concentration of the chemical probe. In this work, we used selective 2’ hydroxyl acylation analyzed by primer extension (SHAPE) and dimethyl sulfate (DMS) chemical probing experiments to explore whether RNA structures are modulated by chemical probe binding events. We find that as the concentration of a chemical probe increases, modified nucleotides locally modulate the RNA structure, resulting in the increase or decrease of chemical probe reactivity in surrounding nucleotides. This cooperative effect is dependent on both chemical probe concentration and size. We find that these cooperative effects can be used to link structurally related nucleotides, and that the cooperative effects result in strikingly different 2D structure predictions as probe concentrations are varied.

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“…In contrast, miR-20b overexpression in LNCaP cells results in decreased cell growth, colony formation and increased apoptosis. Therefore, a different role of miR-20b is suggested depending on the aggressiveness of PCa cell line ( 8 , 43 ). In summary, the exact role of miR-19a/b and miR-20b in prostate cancer has not been clarified to date.…”

Section: Discussionmentioning

confidence: 99%

Epiregulin expression and secretion is increased in castration-resistant prostate cancer

et al. 2023

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IntroductionIn prostate cancer, long-term treatment directed against androgens often leads to the development of metastatic castration-resistant prostate cancer, which is more aggressive and not curatively treatable. Androgen deprivation results in elevated epiregulin expression in LNCaP cells which is a ligand of EGFR. This study aims to reveal the expression and regulation of epiregulin in different prostate cancer stages enabling a more specific molecular characterization of different prostate carcinoma types.MethodsFive different prostate carcinoma cell lines were used to characterize the epiregulin expression on the RNA and protein levels. Epiregulin expression and its correlation with different patient conditions were further analyzed using clinical prostate cancer tissue samples. Additionally, the regulation of epiregulin biosynthesis was examined at transcriptional, post-transcriptional and release level.ResultsAn increased epiregulin secretion is detected in castration-resistant prostate cancer cell lines and prostate cancer tissue samples indicating a correlation of epiregulin expression with tumor recurrence, metastasis and increased grading. Analysis regarding the activity of different transcription factors suggests the involvement of SMAD2/3 in the regulation of epiregulin expression. In addition, miR-19a, -19b, and -20b are involved in post-transcriptional epiregulin regulation. The release of mature epiregulin occurs via proteolytic cleavage by ADAM17, MMP2, and MMP9 which are increased in castration-resistant prostate cancer cells.DiscussionThe results demonstrate epiregulin regulation by different mechanism and suggest a potential role as a diagnostic tool to detect molecular alterations in prostate cancer progression. Additionally, although EGFR inhibitors false in prostate cancer, epiregulin could be a therapeutic target for patients with castration-resistant prostate cancer.

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The dual role of microRNA (miR)-20b in cancers: Friend or foe?

Cited by 15 publications

References 126 publications

LAMC2 regulates proliferation, migration, and invasion mediated by the Pl3K/AKT/mTOR pathway in oral squamous carcinoma

LAMC2 regulates proliferation, migration, and invasion mediated by the Pl3K/AKT/mTOR pathway in oral squamous carcinoma

Cooperativity in RNA chemical probing experiments modulates RNA 2D structure

Epiregulin expression and secretion is increased in castration-resistant prostate cancer

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