Skip to content
2000
Volume 26, Issue 3
  • ISSN: 1389-2010
  • E-ISSN: 1873-4316

Abstract

Aims

This study aims to comprehensively investigate the role of Family Member A with sequence similarity 72-A (FAM72A) in multiple myeloma.

Background

Multiple myeloma poses significant challenges. This study delves into FAM72A's impact on key cellular processes, shedding light on potential therapeutic targets and enhancing our understanding of multiple myeloma progression.

Objectives

Investigate the impact of FAM72A on the proliferation, apoptosis, and bortezomib sensitivity of multiple myeloma cell line U266.

Methods

qRT-PCR analyzed FAM72A expression levels in bone marrow samples from 30 patients with multiple myeloma and 10 healthy donors at the Second Hospital of Shanxi Medical University. Cell lines overexpressing FAM72A were constructed, and Cell Counting Kit 8 (CCK-8) and flow cytometry were used to assess U266 cell proliferation, apoptosis, and sensitivity to bortezomib. Biological predictions for FAM72A were performed to find transcription factors binding to the FAM72A promoter region, verified using a luciferase assay. U266 cells were transfected with si-POU2F2 (POU class 2 homeobox 2), and the impact on cell proliferation was validated. Western blot analysis detected the expression of downstream proteins in the p53 signaling pathway. experiments established a xenograft mouse model further to study the role of FAM72A in multiple myeloma.

Results

FAM72A was upregulated in multiple myeloma bone marrow tissues. Compared to the OE-NC group, the OE-FAM72A group showed increased Mouse Double Minute 2 homolog (MDM2) expression, decreased p53 expression, increased cell proliferation, and decreased apoptosis. POU2F2 was identified as the upstream transcription factor for FAM72A. Compared to the si-NC group, the si-POU2F2 group exhibited decreased MDM2 expression, increased p53 expression, slowed cell proliferation, and increased apoptosis. Silencing POU2F2 could reverse the pro-proliferative effect of over-expressing FAM72A in U266 cells. experiments in a xenograft mouse model further studied the role of FAM72A in multiple myeloma.

Conclusion

Overexpression of FAM72A promotes U266 cell proliferation, inhibits apoptosis, and reduces sensitivity to bortezomib by regulating the POU2F2/FAM72A/p53 signaling pathway.

Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010311258240729080309
2024-08-08
2025-04-13
Loading full text...

Full text loading...

References

  1. Rodriguez-OteroP. PaivaB. San-MiguelJ.F. Roadmap to cure multiple myeloma.Cancer Treat. Rev.202110010228410.1016/j.ctrv.2021.10228434597912
    [Google Scholar]
  2. YuB. JiangT. LiuD. BCMA-targeted immunotherapy for multiple myeloma.J. Hematol. Oncol.202013112510.1186/s13045‑020‑00962‑732943087
    [Google Scholar]
  3. LaganàA. The genome of IMiD-refractory myeloma.Blood2023141656056110.1182/blood.202201846136757732
    [Google Scholar]
  4. ZaalE.A. WuW. JansenG. ZweegmanS. CloosJ. BerkersC.R. Bortezomib resistance in multiple myeloma is associated with increased serine synthesis.Cancer Metab.201751710.1186/s40170‑017‑0169‑928855983
    [Google Scholar]
  5. MurrayM.Y. AugerM.J. BowlesK.M. Overcoming bortezomib resistance in multiple myeloma.Biochem. Soc. Trans.201442480480810.1042/BST2014012625109961
    [Google Scholar]
  6. HoN.T.T. KutznerA. HeeseK. Brain plasticity, cognitive functions and neural stem cells: a pivotal role for the brain-specific neural master gene |-SRGAP2–FAM72-|.Biol. Chem.20173991556110.1515/hsz‑2017‑019028822221
    [Google Scholar]
  7. LiuH. HuangY. ChenY. TangZ. HuangM. MingY. WangM. ChenW. HuangZ. QingL. WangQ. JiaB. Family with Sequence Similarity 72 (FAM72) − A prospective biomarker for poor prognosis in patients with oral squamous cell carcinoma.Arch. Oral Biol.202315110569510.1016/j.archoralbio.2023.10569537086493
    [Google Scholar]
  8. ZhouQ. ChenL. YangL. ZhouH. ChenY. GuoY. Integrated systemic analysis of FAM72A to identify its clinical relevance, biological function, and relationship to drug sensitivity in hepatocellular carcinoma.Front. Oncol.202212104647310.3389/fonc.2022.104647336483027
    [Google Scholar]
  9. GuoC. ZhangX. FinkS.P. PlatzerP. WilsonK. WillsonJ.K.V. WangZ. MarkowitzS.D. Ugene, a newly identified protein that is commonly overexpressed in cancer and binds uracil DNA glycosylase.Cancer Res.200868156118612610.1158/0008‑5472.CAN‑08‑125918676834
    [Google Scholar]
  10. XuY. HirachanS. ShenY. HuangQ. BhandariA. XiaE. The pan‐cancer analysis of the oncogenic role of FAM72A as a BRCA prognostic biomarker and immunotherapeutic target.Environ. Toxicol.20233851100111710.1002/tox.2375136757015
    [Google Scholar]
  11. ZengY. XiongC. TangN. WangS. XiongZ. LiangT. WangQ. LiM. LiJ. FAM72A promotes glioma progression by regulating mitophagy through the Pink1/Parkin signaling pathway.J. Cancer202314690391510.7150/jca.8294937151394
    [Google Scholar]
  12. FuY. JiaX. YuanJ. YangY. ZhangT. YuQ. Fam72a functions as a cell-cycle-controlled gene during proliferation and antagonizes apoptosis through reprogramming PP2A substrates.Developmental Cell.202358539841510.1016/j.devcel.2023.02.006
    [Google Scholar]
  13. García-OrtizA. Rodríguez-GarcíaY. EncinasJ. Maroto-MartínE. CastellanoE. TeixidóJ. Martínez-LópezJ. The role of tumor microenvironment in multiple myeloma development and progression.Cancers202113221710.3390/cancers1302021733435306
    [Google Scholar]
  14. HolthofL.C. van der SchansJ.J. KatsarouA. PoelsR. GelderloosA.T. DrentE. van Hal-van VeenS.E. LiF. ZweegmanS. van de DonkN.W.C.J. ThemeliM. GroenR.W.J. MutisT. Bone marrow mesenchymal stromal cells can render multiple myeloma cells resistant to cytotoxic machinery of CAR T cells through inhibition of apoptosis.Clin. Cancer Res.202127133793380310.1158/1078‑0432.CCR‑20‑218833883175
    [Google Scholar]
  15. GouH. ChenP. WuW. FAM72 family proteins as poor prognostic markers in clear cell renal carcinoma.Biochem. Biophys. Rep.20233510150610.1016/j.bbrep.2023.10150637457361
    [Google Scholar]
  16. ChatonnetF. PignarreA. SérandourA.A. CaronG. AvnerS. RobertN. KassambaraA. LaurentA. BizotM. AgirreX. ProsperF. Martin-SuberoJ.I. MoreauxJ. FestT. SalbertG. The hydroxymethylome of multiple myeloma identifies FAM72D as a 1q21 marker linked to proliferation.Haematologica2020105377478310.3324/haematol.2019.22213331221779
    [Google Scholar]
  17. WangS.M. TieJ. WangW.L. HuS.J. YinJ.P. YiX.F. TianZ.H. ZhangX.Y. LiM.B. LiZ.S. NieY.Z. WuK.C. FanD.M. POU2F2-oriented network promotes human gastric cancer metastasis.Gut20166591427143810.1136/gutjnl‑2014‑30893226019213
    [Google Scholar]
  18. AbdiJ. ChenG. ChangH. Drug resistance in multiple myeloma: Latest findings and new concepts on molecular mechanisms.Oncotarget20134122186220710.18632/oncotarget.149724327604
    [Google Scholar]
  19. KooN. SharmaA.K. NarayanS. Therapeutics targeting p53-MDM2 interaction to induce cancer cell death.Int. J. Mol. Sci.2022239500510.3390/ijms2309500535563397
    [Google Scholar]
  20. HeeseK. The protein p17 signaling pathways in cancer.Tumour Biol.20133464081408710.1007/s13277‑013‑0999‑123900679
    [Google Scholar]
  21. LiuE. SudhaP. BeckerN. JaouadiO. SuvannasankhaA. LeeK. AbonourR. Abu ZaidM. WalkerB.A. Identifying novel mechanisms of biallelic TP53 loss refines poor outcome for patients with multiple myeloma.Blood Cancer J.202313114410.1038/s41408‑023‑00919‑237696786
    [Google Scholar]
  22. WangQ. ShiQ. ChenY. WangG. ShenL. Recombinant human p53 adenovirus injection combined with Bortezomib inhibits proliferation and promotes apoptosis in multiple myeloma.Leuk. Res.202312710704110.1016/j.leukres.2023.10704136801701
    [Google Scholar]
  23. ChangY.T. ChiuI. WangQ. BustamanteJ. JiangW. RycajK. YiS. LiJ. Kowalski-MueggeJ. MatsuiW. Loss of p 53 enhances the tumor-initiating potential and drug resistance of clonogenic multiple myeloma cells.Blood Adv.20237143551356010.1182/bloodadvances.202200938737042949
    [Google Scholar]
  24. CliftonL.A. Wacklin-KnechtH.P. ÅdénJ. MushtaqA.U. SparrmanT. GröbnerG. Creation of distinctive Bax-lipid complexes at mitochondrial membrane surfaces drives pore formation to initiate apoptosis.Sci. Adv.2023922eadg794010.1126/sciadv.adg794037267355
    [Google Scholar]
  25. DolkaI. KrólM. SapierzyńskiR. Evaluation of apoptosis-associated protein (Bcl-2, Bax, cleaved caspase-3 and p53) expression in canine mammary tumors: An immunohistochemical and prognostic study.Res. Vet. Sci.201610512413310.1016/j.rvsc.2016.02.00427033920
    [Google Scholar]
  26. YuY. WangZ. ZhengQ. LiJ. FAM72 serves as a biomarker of poor prognosis in human lung adenocarcinoma.Aging20211368155817610.18632/aging.20262533686947
    [Google Scholar]
  27. BaiY. CaoK. ZhangP. MaJ. ZhuJ. Prognostic and immunological implications of FAM72A in pan-cancer and functional validations.Int. J. Mol. Sci.202224137510.3390/ijms2401037536613817
    [Google Scholar]
/content/journals/cpb/10.2174/0113892010311258240729080309
Loading
/content/journals/cpb/10.2174/0113892010311258240729080309
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keyword(s): apoptosis; FAM72A; Multiple myeloma; p53; POU2F2; therapeutic targets
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test