Effect of Mimic Hypoxia on the Proliferation and Expression of miR-27a, miR-9, miR-370 and their Target Genes in MOLT-4 and KG1a Cell Lines

OBJECTIVE: The aim of this study was to investigate the effect of mimic hypoxia on proliferation, the expression of significant miRNAs, and genes involved in drug resistance in MOLT-4 and KG1 cell lines.

MATERIALS AND METHODS: The KG1 and MOLT-4 cell lines were cultured in RPMI 1640 medium supplemented with 20% FBS and 10% FBS respectively. The MTT test was used for determining  the optimum dose of CoCl2 for KG1 and MOLT-4 cell lines. Western blotting was used for the detection of HIF-1a protein and the confirmation of mimic hypoxia induced by CoCl2. For evaluating the effect of mimic hypoxia on proliferation of MOLT-4 and KG1 cell lines, cell counting was done using trypan blue at 24, 48, and 72 hours. Furthermore, the results obtained from cell counting were confirmed with the MTT test. Total RNA was extracted  using the RNX Plus solution kit according to the manufacturer's protocol. The expression of genes and miRNAs was evaluated with real time PCR.

RESULTS: According to this study, mimic hypoxia induced by CoCl2 contributes to the overexpression of drug resistance related genes including MDR1, MRP1, FOXM1, BCL-xl genes, and the suppression of PUMA gene compared to the control group. The results also showed that mimic hypoxia condition leads to the up-regulation of miR-9 and down-regulation of miR-27a and miR-370. Additionally, our outcomes demonstrated that mimic hypoxia has an inhibitory effect on the proliferation of MOLT-4 and KG1 cell lines.

CONCLUSION: Treatment with CoCl2 has an inhibitory effect on the proliferation of MOLT-4 and KG1 cell lines independent from real hypoxia. Additionally, mimic hypoxia has a substantial effect on the expression of  genes and miRNAs involved in drug resistance. Finally, we are still far away to discover the exact functional mechanisms of hypoxia on drug resistance but these evaluations can provide new perspectives into this field for the upcoming studies.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:22

Enthalten in:

Asian Pacific journal of cancer prevention : APJCP - 22(2021), 6 vom: 01. Juni, Seite 1975-1984

Sprache:

Englisch

Beteiligte Personen:

Emaogolizadeh Gurd Tapeh, Behnam [VerfasserIn]
Mohammadi, Ali [VerfasserIn]
Alivand, Mohammad Reza [VerfasserIn]
Solali, Saeed [VerfasserIn]

Links:

Volltext

Themen:

3G0H8C9362
ALL
AML
Cancer
Cobalt
Cobaltous chloride
Drug resistance
EVS87XF13W
Journal Article
MicroRNAs
Mimic hypoxia

Anmerkungen:

Date Completed 07.12.2021

Date Revised 14.12.2021

published: Electronic

Citation Status MEDLINE

doi:

10.31557/APJCP.2021.22.6.1975

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM327283823