Skip to main content

Advertisement

SpringerLink
Log in

Systems biology approach: identification of hub genes, signaling pathways, and molecular docking of COL1A1 gene in cervical insufficiency

  • Original Research
  • Published:
In Silico Pharmacology Aims and scope Submit manuscript

Abstract

The collagen type I alpha 1 (COL1A1, OMIM #120,150) gene, encoding the alpha-1 chain of type I collagen (UniProt #P02452), plays a key role in life-homeostasis due to its remarkable involvement in collagen synthesis. It is a promising candidate gene implicated in the pathogenesis of cervical insufficiency (CI). This study aimed to identify genetic variations within the COL1A1 gene that contribute to the development of CI. Polymerase chain reaction (PCR) and amplicon sequencing were implemented for single nucleotide polymorphisms (SNPs) detection (+ 1245G/T, SP1 rs1800012), which revealed wild-type sequence for targeted SNPs in enrolled proband indicated negative results regarding COL1A1 gene involvement for current form of CI. It allows further investigation of other closely connected genes probed in this study. Computational approaches viz. Protein-protein interaction (PPI), gene ontology (GO), and pathway participation were used to identify the crucial hub genes and signaling pathways for COL1A1 and CI. Using the Yet Another Scientific Artificial Reality Application (YASARA) software, molecular docking, and molecular dynamic (MD) simulation with the oxytocin (CID 439,302), estradiol (CID 129,728,744), progesterone (CID 5994) and hydroxyprogesterone (CID 150,788) were done. Interactive bioinformatics analysis demonstrated that the COL1A1 and more than 10 collagen sister genes had a strong connection with CI. In sum, the findings of this study provide insights into a modus operandi that can be utilized to illuminate the path toward studying sister genes and smooth diagnosis of CI. These findings have implications for understanding the foundational process of the condition and potentially developing screening, diagnostic, and therapeutic interventions.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

Data availability

No datasets were generated or analysed during the current study.

References

  • ACOG Practice Bulletin 142 No. (2014) Cerclage for the management of cervical insufficiency. Obstet Gynecol 123(2 Pt 1):372–379

    Google Scholar 

  • Ahmad S, Raza K (2023) Identification of 5-nitroindazole as a multitargeted inhibitor for CDK and transferase kinase in lung cancer: a multisampling algorithm-based structural study. Mol Diversity, 1–14

  • Alegina EV, Tetruashvili NK, Agadzhanova AA, Trofimov DY, Donnikov AE (2016) Role of collagen gene polymorphisms in the structure of early gestation loss. Bull Exp Biol Med 160:360–363

  • Alves APV, Freitas AB, Levi JE, Amorim Filho AG, Franco LA, Hoshida MS, Carvalho MHB (2021) COL1A1, COL4A3, TIMP2 and TGFB1 polymorphisms in cervical insufficiency. J Perinat Med 49(5):553–558

    Article  CAS  PubMed  Google Scholar 

  • American Pregnancy Association (2021) Cervical insufficiency. Retrieved from https://americanpregnancy.org/infertility/cervical-insufficiency/

  • Anum EA, Hill LD, Pandya A, Strauss III, J. F (2009) Connective tissue and related disorders and PTB birth: clues to genes contributing to prematurity. Placenta 30(3):207–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Batista, N. C., Bortolini, M. A., Silva, R. S., Teixeira, J. B., Melo, N. C., Santos,R. G., … Castro, R. A. (2020). Collagen I and collagen III polymorphisms in women with pelvic organ prolapse. Neurourology and Urodynamics, 39(7), 1977–1984

  • Blanks AM, Thornton S (2003) The role of oxytocin in parturition. BJOG: Int J Obstet Gynecol 110:46–51

    Article  CAS  Google Scholar 

  • Byers, P. H., Belmont, J., Black, J., De Backer, J., Frank, M., Jeunemaitre, X., …Wheeldon, N. (2017, March). Diagnosis, natural history, and management in vascular Ehlers–Danlos syndrome. In American Journal of Medical Genetics Part C: Seminars in Medical Genetics (Vol. 175, No. 1, pp. 40–47)

  • Carbonare LD, Valenti MT, Zanatta M, Donatelli L, Cascio L, V (2009) Circulating mesenchymal stem cells with abnormal osteogenic differentiation in patients with osteoporosis. Arthritis Rheumatism: Official J Am Coll Rheumatol 60(11):3356–3365

    Article  Google Scholar 

  • Challis JR, Lye SJ, Gibb W, Whittle W, Patel F, Alfaidy N (2001) Understanding preterm labor. Ann N Y Acad Sci 943(1):225–234

    Article  CAS  PubMed  Google Scholar 

  • Chibbar R, Miller FD, Mitchell BF (1993) Synthesis of oxytocin in amnion, chorion and decidua may influence the timing of human parturition. J Clin Invest 185 – 92. 67.

  • Chibbar R, Wong S, Miller FD, Mitchell BF (1995) Estrogen stimulates oxytocin gene expression in human fetal membranes and decidua. J Clin Endocrinol Metab 80:567–572

    CAS  PubMed  Google Scholar 

  • Durstewitz G, Polley A, Plieske J, Luerssen H, Graner EM, Wieseke R, Ganal MW (2010) SNP discovery by amplicon sequencing and multiplex SNP genotyping in the allopolyploid species Brassica napus. Genome 53(11):948–956

    Article  CAS  PubMed  Google Scholar 

  • Erlich HA, Gelfand D, Sninsky JJ (1991) Recent advances in the polymerase chain reaction. Science 252(5013):1643–1651

    Article  CAS  PubMed  Google Scholar 

  • Fischer GM, Swain ML (1985) Effects of estradiol and progesterone on the increased synthesis of collagen in atherosclerotic rabbit aortas. Atherosclerosis 54(2):177–185

    Article  CAS  PubMed  Google Scholar 

  • Fuchs F, Audibert F, Senat MV (2014) Progesterone and PTB delivery: back to the future? Gynecologie Obstetrique Fertil 42(2):112–122

    Article  CAS  Google Scholar 

  • Gedikbasi A, Yücel B, Arslan O, Giris M, Gedikbasi A, Abbasoglu SD (2016) Dynamic collagen changes in cervix during the first trimester and decreased collagen content in cervical insufficiency. J Maternal-Fetal Neonatal Med 29(18):2968–2972

    Article  CAS  Google Scholar 

  • Goldenberger D, Perschil I, Ritzler M, Altwegg M (1995) A simple universal DNA extraction procedure using SDS and proteinase K is compatible with direct PCR amplification. Genome Res 4(6):368–370

    Article  CAS  Google Scholar 

  • Kadler KE, Baldock C, Bella J (1955) Boot--Handford, R. P. Collagens at a glance. J Cell Sci, 120

  • Leikina E, Mertts MV, Kuznetsova N, Leikin S (2002) Type I collagen is thermally unstable at body temperature. Proc Natl Acad Sci 99(3):1314–1318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li C, Zeng X, Yu H et al (2018) Identification of hub genes with diagnostic values in pancreatic cancer by bioinformatics analyses and supervised learning methods. World J Surg Oncol 16(1):223

    Article  PubMed  PubMed Central  Google Scholar 

  • Marini, J. C., Forlino, A., Cabral, W. A., Barnes, A. M., San Antonio, J. D., Milgrom,S., … Byers, P. H. (2007). Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Human mutation, 28(3), 209–221

  • Mastrolia SA, Baumfeld Y, Hershkovitz R, Yohay D, Trojano G, Weintraub AY (2018) Independent association between uterine malformations and cervical insufficiency: a retrospective population-based cohort study. Arch Gynecol Obstet 297:919–926

    Article  PubMed  Google Scholar 

  • Minamoto T, Arai K, Hirakawa S, Nagai Y (1987) Immunohistochemical studies on collagen types in the uterine cervix in pregnant and nonpregnant states. Am J Obstet Gynecol 156:138–144

    Article  CAS  PubMed  Google Scholar 

  • Norwitz ER, Caughey AB (2011) Progesterone supplementation and the prevention of preterm birth. Reviews Obstet Gynecol 4(2):60

    Google Scholar 

  • Papatsonis D, Flenady V, Cole S, Liley H (2005) Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database Syst Rev, (3)

  • Ranganath P, Laine CM, Gupta D, Mäkitie O, Phadke SR (2011) COL1A1 mutation in an Indian child with Caffey disease. Indian J Pediatr 78:877–879

    Article  PubMed  Google Scholar 

  • Romero, R., Edwards, D. R. V., Kusanovic, J. P., Hassan, S. S., Mazaki-Tovi, S., Vaisbuch,E., … Menon, R. (2010). Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous PTB labor with intact membranes.American journal of obstetrics and gynecology, 202(5), 431–e1

  • Romero R, Yeo L, Miranda J, Hassan SS, Conde-Agudelo A, Chaiworapongsa T (2013) A blueprint for the prevention of preterm birth: vaginal progesterone in women with a short cervix. J Perinat Med 41(1):27–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shao-Wei WANG, Lin-Lin MA, Huang S, Liang L, ZHANG JR (2016) Role of cervical cerclage and vaginal progesterone in the treatment of cervical incompetence with/without PTB Birth History. Chin Med J, 2670–2675

  • Sheyn D, Addae-Konaedu KL, Bauer AM, Dawodu KI, Hackney DN, El-Nashar SA (2018) History of cervical insufficiency increases the risk of pelvic organ prolapse and stress urinary incontinence in parous women. Maturitas 107:63–67

    Article  PubMed  Google Scholar 

  • Singh S, Baker QB, Singh DB (2022) Molecular docking and molecular dynamics simulation. Bioinformatics. Academic, pp 291–304

  • Sundtoft I, Uldbjerg N, Steffensen R, Sommer S, Christiansen OB (2016) Polymorphisms in genes coding for cytokines, mannose-binding lectin, collagen metabolism and thrombophilia in women with cervical insufficiency. Gynecol Obstet Invest 81(1):15–22

    Article  CAS  PubMed  Google Scholar 

  • Sundtoft I, Langhoff-Roos J, Sandager P, Sommer S, Uldbjerg N (2017) Cervical collagen is reduced in non‐pregnant women with a history of cervical insufficiency and a short cervix. Acta Obstet Gynecol Scand 96(8):984–990

    Article  CAS  PubMed  Google Scholar 

  • Svensson AC, Sandin S, Cnattingius S, Reilly M, Pawitan Y, Hultman CM, Lichtenstein P (2009) Maternal effects for PTB birth: a genetic epidemiologic study of 630,000 families. Am J Epidemiol 170(11):1365–1372

    Article  PubMed  Google Scholar 

  • Tilkeridis C, Bei T, Garantziotis S, Stratakis CA (2005) Association of a COL1A1 polymorphism with lumbar disc disease in young military recruits. J Med Genet 42(7):e44–e44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tita ATN, Rouse DJ (2009) Progesterone for preterm birth prevention: an evolving intervention. Am J Obstet Gynecol 200(3):219–224

    Article  CAS  PubMed  Google Scholar 

  • Trivedi PG, Gajera JB, Ghanchi FI, Sindhav GM (2023) Simultaneous detection of thirteen exons of dystrophin gene by optimized multiplex PCR assay to screen Duchenne/Becker muscular dystrophy

  • Volozonoka L, Rots D, Kempa I, Kornete A, Rezeberga D, Gailite L, Miskova A (2020) Genetic landscape of PTB birth due to cervical insufficiency: comprehensive gene analysis and patient next-generation sequencing data interpretation. PLoS ONE, 15(3), e0230771

  • Wang SW, Ma LL, Huang S, Liang L, Zhang JR (2016) Role of cervical cerclage and vaginal progesterone in the treatment of cervical incompetence with/without PTB birth history. Chin Med J 129(22):2670–2675

    Article  PubMed  PubMed Central  Google Scholar 

  • Warren JE, Silver RM, Dalton J, Nelson LT, Branch DW, Porter TF (2007) Collagen 1Α1 and transforming growth factor-β polymorphisms in women with cervical insufficiency. Obstet Gynecol 110(3):619–624

    Article  CAS  PubMed  Google Scholar 

  • Wilcox AJ, Skjærven R, Lie RT (2008) Familial patterns of PTB delivery: maternal and fetal contributions. Am J Epidemiol 167(4):474–479

    Article  PubMed  Google Scholar 

  • Yang W, Zhao X, Han Y et al (2019) Identification of hub genes and therapeutic drugs in esophageal squamous cell carcinoma based on integrated bioinformatics strategy. Cancer Cell Int 19:142

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The author, Pooja Trivedi would like to thank the Department of Science and Technology (DST), New Delhi for providing the SRF-INSPIRE fellowship (IF190292). Faizal Ghanchi would like to thank the Department of Biotechnology (DBT), New Delhi for providing the JRF fellowship (1938).

Funding

This research did not receive any specific grant.

Author information

Authors and Affiliations

  1. Smt. NHL Municipal Medical College, Pritan Rai Cross Road, Ellise Bridge, Paldi, Ahmedabad, Gujarat, 380006, India

    Sushma Shah

  2. Department of Zoology, BMT, HGC and WBC, University School of Sciences, Gujarat University, Ahmedabad, 09, Gujarat, India

    Pooja Trivedi, Mohammadfesal Ghanchi, Gaurang Sindhav & Ramtej J. Verma

  3. FICOG, Diploma (USG), PGCML, PGDMLS, PGDCR, PGDHHM Prof. & HOD ObGy, GCSMCH & RC, Opp. DRM Office, Chamunda Bridge, Naroda Road, Ahmedabad, 380025, India

    Haresh Doshi

Authors
  1. Sushma Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pooja Trivedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammadfesal Ghanchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gaurang Sindhav
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haresh Doshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ramtej J. Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PT and MG performed practicals and in silico study, wrote the main text. GS framed and reviewed the manuscript. All authors have participated equally in this research, and took the responsibility for the decision to submit for publication. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Gaurang Sindhav.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shah, S., Trivedi, P., Ghanchi, M. et al. Systems biology approach: identification of hub genes, signaling pathways, and molecular docking of COL1A1 gene in cervical insufficiency. In Silico Pharmacol. 12, 45 (2024). https://doi.org/10.1007/s40203-024-00218-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40203-024-00218-z

Keywords

Search

Navigation