Peptidyl–Prolyl &lt;i&gt;cis&lt;/i&gt;/&lt;i&gt;trans&lt;/i&gt; Isomerase NIMA-Interacting 1 as a Therapeutic Target in Hepatocellular Carcinoma

Kım, Garam; Kim, Jin Young; Choi, Hong Seok

doi:10.1248/bpb.b15-00245

Cited by 8 publications

(5 citation statements)

References 54 publications

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“…PPIase family proteins are isomerases that shuffle disulfide bonds and allow proinsulin molecules to potentially reach their native conformation. Peptidyl-prolyl cis-trans isomerase b (PPIB) is a member of the cyclophilin-type PPIase family and contributes to protein folding ( 14 – 16 ). If proinsulin is not properly folded within the ER, ER stress-induced cell apoptosis occurs.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells

Wei

Zhu²,

Feng

et al. 2018

Exp Ther Med

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Cyclosporin A (CsA) is widely used as an immunosuppressor in the context of organ transplantation or autoimmune disorders. Recent studies have revealed the detrimental effects of CsA on insulin resistance and pancreatic β cell failure; however, the molecular mechanisms are unknown. The present study sought to confirm the associations between CsA and β cell failure, and to investigate the roles of proinsulin folding and endoplasmic reticulum (ER) stress in CsA-induced β cell failure. The viability of MIN6 cells treated with CsA was evaluated with MTT assay. Expression levels of insulin, peptidyl-prolyl cis-trans isomerase B (PPIB), cleaved caspase-3, phospho-protein kinase R (PKR)-like endoplasmic reticulum kinase (p-PERK), PKR-like endoplasmic reticulum kinase (PERK), binding immunoglobulin protein (BIP), and C/EBP homologous protein (CHOP) were detected via reducing western blot assay. Non-reducing western blot analysis was performed to examine the expression of misfolded proinsulin peptides. The proliferation of MIN6 cells was not inhibited by CsA at concentrations <1 µmol/l. CsA treatment resulted in the decreased expression of insulin and PPIB; however, it also increased the phosphorylation of PERK, and upregulated the expression of PERK, BIP, CHOP and cleaved caspase-3. The results indicated that CsA could induce pancreatic β cell dysfunction and the potential mechanism underlying this phenomenon may be PPIB-associated proinsulin misfolding, which in turn induces ER stress in β cells.

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Section: Introductionmentioning

confidence: 99%

Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells

Wei

Zhu²,

Feng

et al. 2018

Exp Ther Med

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“…The PPIase family consists of broadly expressed enzymes that could accelerate the cis-trans proline peptide bonds isomerization. 32 PPIB, a member of the PPIase family, has been found to contribute to protein folding, 8 and its recessive mutations may result in multi-different phenotypes ranging from lethality in the perinatal period to severe deformation in osteogenesis imperfecta. 33 However, its relation with miRNAs was scarcely discussed.…”

Section: Discussionmentioning

confidence: 99%

“…PPIB (cyclophilin B, CypB), a member of the PPIase family, has been found to contribute to protein folding. 8 In cancer biology, as Choi et al pointed out, PPIB is related to malignant progression and regulation of genes. 9 As for HCC, Kim et al revealed that hypoxia-induced PPIB can stimulate HCC cell survival via a positive feedback loop with hypoxia-inducible factor-1α (HIF-1α).…”

Section: Introductionmentioning

confidence: 99%

Ultrasound-Targeted Microbubble Destruction-Mediated miR-206 Overexpression Promotes Apoptosis and Inhibits Metastasis of Hepatocellular Carcinoma Cells Via Targeting PPIB

Xie

Yang

et al. 2020

Technol Cancer Res Treat

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Background: Ultrasound-targeted microbubble destruction (UTMD) has been found to be an effective method for delivering microRNAs (miRNAs, miRs). The current study is aimed at discovering the potential anti-cancer effects of UTMD-mediated miR-206 on HCC. Methods: In our study, the expressions of miR-206 and peptidyl-prolyl cis-trans isomerase B (PPIB) in HCC tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). PPIB expressions in HCC and adjacent normal tissues were analyzed by gene expression profiling interactive analysis (GEPIA). MiR-206 mimic and mimic control were transfected into HCC cells using UTMD. Potential binding sites between miR-206 and PPIB were predicted and confirmed by TargetScan and dual-luciferase reporter assay, respectively. Cell migration, invasion, and apoptosis were detected by wound healing assay, Transwell, and flow cytometry, respectively. The expressions of apoptosis-related proteins (Bax, Bcl-2), Epithelial-to-mesenchymal (EMT) markers (E-cadherin, N-cadherin and Snail) and PPIB were measured by Western blot. Results: MiR-206 expression was downregulated while PPIB expression was upregulated in HCC, and PPIB was recognized as a target gene of miR-206 in HCC tissues. UTMD-mediated miR-206 inhibited HCC cell migration and invasion while promoting apoptosis via regulating the expressions of proteins related to apoptosis, migration, and invasion by targeting PPIB. Conclusion: Our results suggested that the delivery of UTMD-mediated miR-206 could be a potential therapeutic method for HCC treatment, given its effects on inhibiting cell migration and invasion and promoting cell apoptosis.

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“…Pin1 binds to the JNK-mediated Ser57 phosphorylation of the HIV-1 integrase, stabilizing its structure and further promoting integration . In addition to HIV, Pin1 is also involved in other viral infections, including hepatitis B virus (HBV), , hepatitis C virus (HCV), Epstein–Barr virus (EBV), , human T-cell leukemia virus type 1 (HTLV-1), , and high-risk human papillomavirus (HR-HPV) …”

Section: Pin1 and Human Diseasesmentioning

confidence: 99%

Biological Function of Pin1 in Vivo and Its Inhibitors for Preclinical Study: Early Development, Current Strategies, and Future Directions

Jin

et al. 2023

J. Med. Chem.

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Peptidyl-prolyl cis/trans isomerase family (PPIase) is structurally divided into three subfamilies, cyclophilins (Cyps), FK506-binding proteins (FKBPs), and parvulins. Pin1 belongs to the parvulin family and is the only enzyme capable of isomerizing the phosphorylated Ser/Thr-Pro motif (p-Ser/Thr-Pro) in its interacting proteins. Due to its multibiological functions in vivo, including folding, intracellular signaling, transcription, cell cycle progression, and apoptosis, Pin1 is extensively studied as a promising drug target for various human diseases, especially cancer. In this Perspective, we summarized the literature covering diverse classes of Pin1 inhibitors and the inhibition mechanism, aiming to provide insights for the design of potent Pin1 inhibitors and suggest alternative strategies for developing potent Pin1 inhibitors.

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Peptidyl–Prolyl <i>cis</i>/<i>trans</i> Isomerase NIMA-Interacting 1 as a Therapeutic Target in Hepatocellular Carcinoma

Cited by 8 publications

References 54 publications

Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells

Inhibition of peptidyl‑prolyl cis‑trans isomerase B mediates cyclosporin A‑induced apoptosis of islet β cells

Ultrasound-Targeted Microbubble Destruction-Mediated miR-206 Overexpression Promotes Apoptosis and Inhibits Metastasis of Hepatocellular Carcinoma Cells Via Targeting PPIB

Biological Function of Pin1 in Vivo and Its Inhibitors for Preclinical Study: Early Development, Current Strategies, and Future Directions

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