Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
İnsan Akciğer Kanserlerinde TRPM Gen ve Piezo İyon Kanallarının Ekspresyonu
Expression of TRPM Gene and Piezo Ion Channels in Human Lung Cancers
Suna POLATOĞLUa, Akın Eraslan BALCIa, Ebru ÖNALANb, Ahmet TEKTEMURa, Muharrem ÇAKMAKa
aGöğüs Cerrahisi AD,
bTıbbi Biyoloji ve Genetik AD, Fırat Üniversitesi Tıp Fakültesi, Elazığ, TÜRKİYE
Turkiye Klinikleri J Med Sci. 2019;39(1):26-32
doi: 10.5336/medsci.2018-61895
Article Language: TR
Full Text
ÖZET
 Amaç: İyon kanalları apopitozis, proliferasyon, farklılaşma gibi hücre süreçlerinde görevli olup, transient reseptör potansiyel melastatin (TRPM) katyon kanalları ve kalsiyum homeostazı tarafından kontrol edilirler. İyon kanallarının aktivasyonu, otofajik aktiviteyi bloke, blokajı ise otofajik aktiviteyi arttırarak kanser hücresi gelişimini engeller. Çalışmamızda, kanserli akciğer dokusunda, TRPM 2, 4, 5, 7, 8 ve Piezo 1, 2 iyon kanallarının ekspresyonlarında artış olup olmadığı ve bunun otofajik aktivite üzerindeki etkisini göstermeyi amaçladık. Böylece, aktive olan iyon kanalları bloke edilerek, otofajik aktivite artışının sağlanabileceğini ve akciğer kanserli hastalarda bir tedavi seçeneği olabileceğini düşünmekteyiz. Gereç ve Yöntemler: Kırk adet kanserli, 10 adet normal akciğer dokusu çalışılmaya alındı. Sırasıyla, total RNA izolasyonu, spektrofotometrik RNA ölçümü, komplementer DNA sentezi, high-capacity cDNA rivörs transkripsiyonla elde edilen cDNA'lar, spesifik primerlerin varlığında real time-polimeraz zincir reaksiyonuyla amplifiye edildi. Gliseraldehit 3-fosfat dehidrogenaz, TRPM 2, 4, 5, 7, 8, Piezo1, 2 genleri belirlendi. Seviyeleri ölçüldü. Bulgular: Kanserli hastaların 29'u erkek, 8'i kadın, yaş ortalaması 60, 21 yıl idi. Kontrol grubunun 8'i erkek, 2'si kadın, yaş ortalaması 63,42 yıl idi. Kontrol grubuna göre adenokarsinom, epidermoid, küçük hücreli kanser gruplarında TRPM5 mRNA?nın; epidermoid karsinom, küçük hücreli kanser gruplarında ise TRPM7 mRNA'nın arttığı belirlendi. Piezo1 mRNA'nın adenokarsinomların %20'sinde, epidermoid karsinomların %15'inde, küçük hücreli kanserlerin sadece 1'inde pozitif olduğu görüldü. Piezo2 mRNA'nın adenokarsinom, epidermoid ve küçük hücreli akciğer kanserlerinde anlamlı düzeyde arttığı saptandı. Sonuç: Akciğer kanserinde, otofajik aktivite kaybı TRPM, Piezo iyon kanalları ile ilişkilidir. Bu kanallar terapötik bir hedef olarak alındığında, akciğer kanseri tedavisinde önemli bir süreç başlatacaktır.

Anahtar Kelimeler: Akciğer kanseri; TRPM kanalları; Piezo 1; Piezo 2
ABSTRACT
 Objective: Ions channels are responsible for cell processes such as apoptosis, proliferation, differentiation and are controlled by transient receptor potential melastatin (TRPM) cation channels and calcium homeostasis. Activation of ion channels facilitates cancer cell development by blocking autophagic activity. Blockage increases the autophagic activity and prevents cancer cell development. In our study, we aimed to Show whether there is an increase in the expression of TRPM 2, 4, 5, 7, 8 and Piezo 1, 2 ion channels in cancerous lung tissue and its effect on autophagic activity. Thus, these channels can be considered as a therapeutic target for increased autophagic activity. Material and Methods: Forty cancers and 10 normal lung tissues were taken into work. cDNAs obtained by total RNA isolation, spectrophotometric RNA measurement, complementary DNA synthesis, high-capacity cDNA reverse transcription were amplified by real timepolymerase chain reaction in the presence of sequence-specific primers. Glyceraldehyde 3-phosphate dehydrogenase, TRPM 2, 4, 5, 7, 8, Piezo1, 2 genes were identified. Results: Twentynine of the cancer patients were male, 8 were female. Eight of the control group were male, 2 were female. 15 of the cancer patients have epidermoid, 16 adeno, 3 large cell, 3 small cell carcinoma. According to the control group, TRPM5 mRNA increased was seen in adenocarcinoma, epidermoid, small cell cancer groups. In the epidermoid carcinoma and small cell carcinoma groups, increase in TRPM7 mRNA was determined. Piezo1 mRNA was found to be positive in 20% of adenocarcinomas, 15% of epidermoid carcinomas and only 1 of small cell cancers. Piezo2 mRNA was significantly increased in adenocarcinoma, epidermoid, and small cell lung cancer. Conclusion: The loss of autophagic activity in lung cancer is associated with TRPM and piezo ion channels. When these channels are taken as a therapeutic target, they will initiate an important process in lung cancer treatment.

Keywords: Lung cancer; TRPM channels; Piezo 1; Piezo 2
REFERENCES:
  1. Jiang BH, Liu LZ. PI3K/PTEN signaling in tumorigenesis and angiogenesis. Biochem Biophys Acta. 2008;1784(1):150-8. [Crossref]
  2. Gautier M, Dhennin-Duthille I, Ay AS, Rybarczyk P, Korichneva I, Ouadid-Ahidouch H. New insights into pharmacological tools to TR(i)P cancer up. Br J Pharmacol. 2014; 171(10):2582-92. [Crossref] [PMC]
  3. Santoni G, Farfariello V, Amantini C. TRPV channels in tumor growth and progression. Adv Exp Med Biol. 2011;704(4):947-67. [Crossref]
  4. Shapovalov G, Lehen?kyi V, Skryma R, Prevarskaya N. TRP channels in cell survival and cell death in normal and transformed cells. Cell Calcium. 2011;50(3):295-302. [Crossref]
  5. Lazzeri M, Costantini E, Porena M. TRP family proteins in the lower urinary tract: translating basic science into new clinical prospective. Ther Adv Urol. 2009;1(1):33-42. [Crossref] [PMC]
  6. Guilbert A, Gautier M, Dhennin-Duthille I, Rybarczyk P, Sahni J, Sevestre H, et al. Transient receptor potential melastatin 7 is involved in oestrogen receptor-negative metastatic breast cancer cells migration through its kinase domain. Eur J Cancer. 2013;49(17):3694-707. [Crossref]
  7. Middelbeek J, Kuipers AJ, Henneman L, Visser D, Eidhof I, van Horssen R, et al. TRPM7 is required for breast tumor cell metastasis. Cancer Res. 2012;72(16):4250-61. [Crossref]
  8. Trapani V, Arduini D, Cittadini A, Wolf FI. From magnesium to magnesium transporters in cancer: TRPM7, a novel signature in tumour development. Magnes Res. 2013;26(4):14955.
  9. Baldoli E, Maier JA. Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells. Angiogenesis. 2012;15(1):47-57. [Crossref]
  10. Kim BJ, Nah SY, Jeon JH, So I, Kim SJ. Transient receptor potential melastatin 7 channels are involved in ginsenoside Rg3-induced apoptosis in gastric cancer cells. Basic Clin Pharmacol Toxicol. 2011;109(4):233-9. [Crossref]
  11. Zhang L, Barritt GJ. TRPM8 in prostate cancer cells: a potential diagnostic and prognostic marker with a secretory function? Endocr Relat Cancer. 2006;13(1):27-38. [Crossref]
  12. Clapham DE, Montell C, Schultz G, Julis D; International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels. Pharmacol Rev. 2003;55(4):591-6. [Crossref]
  13. Schönherr R. Clinical relevance of ion channels for diagnosis and therapy of cancer. J Membr Biol. 2005;205(3):175-84. [Crossref]
  14. Prevarskaya N, Zhang L, Barritt G. TRP channels in cancer. Biochim Biophys Acta. 2007;1772(8):937-46. [Crossref]
  15. Prawitt D, Enklaar T, Klemm G, Gärtner B, Spangenberg C, Winterpacht A, et al. Identification and characterization of MTR1, a novel gene with homology to melastatic (MLSN1) and the TRP gene family located in the BWSWT2 critical region on chromosome 11p15.5 and showing allele-specific expression. Hum Mol Genet. 2000;9(2):203-16. [Crossref]
  16. Parajuli SP, Hristov KL, Sullivan MN, Xin W, Smith AC, Earley S, et al. Control of urinary bladder smooth muscle excitability by the TRPM4 channel modulator 9-phenanthrol. Channels (Austin). 2013;7(2):537-40. [Crossref] [PMC]
  17. Suguro M, Tagawa H, Kagami Y, Okamoto M, Ohshima K, Shiku H, et al. Expression profiling analysis of the CD5+ diffuse large B-cell lymphoma subgroup: development of a CD5 signature. Cancer Sci. 2006;97(9):868-74. [Crossref]
  18. Simon F, Varela D, Cabello-Verrugio C. Oxidative stress-modulated TRPM ion channels in cell dysfunction and pathological conditions in humans. Cell Signal. 2013;25(7):1614-24. [Crossref]
  19. Orfanelli U, Wenke AK, Doglioni C, Russo V, Bosserhoff AK, Lavorgna G. Identification of novel sense and antisense transcription at the TRPM2 locus in cancer. Cell Res. 2008; 18(11):1128-40. [Crossref]
  20. Xiao R, Xu XZ. Mechanosensitive channels: in touch with Piezo. Curr Biol. 2010;20(21):R936-8. [Crossref] [PMC]
  21. McHugh BJ, Buttery R, Lad Y, Banks S, Haslett C, Sethi T. Integrin activation by Fam38A uses a novel mechanism of R-Ras targeting to the endoplasmic reticulum. J Cell Sci. 2010;123(Pt 1):51-61. [Crossref]

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