Open Access

Combination of miR‑143 and miR‑506 reduces lung and pancreatic cancer cell growth through the downregulation of cyclin‑dependent kinases

  • Authors:
    • A.K.M. Nawshad Hossian
    • Gerardo G. Mackenzie
    • George Mattheolabakis
  • View Affiliations

  • Published online on: January 27, 2021     https://doi.org/10.3892/or.2021.7953
  • Article Number: 2
  • Copyright: © Hossian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung cancer (LC) and pancreatic cancer (PC) are the first and fourth leading causes of cancer‑related deaths in the US. Deregulated cell cycle progression is the cornerstone for rapid cell proliferation, tumor development, and progression. Here, we provide evidence that a novel combinatorial miR treatment inhibits cell cycle progression at two phase transitions, through their activity on the CDK4 and CDK1 genes. Following transfection with miR‑143 and miR‑506, we analyzed the differential gene expression of CDK4 and CDK1, using qPCR or western blot analysis, and evaluated cell cycle inhibition, apoptosis and cytotoxicity. The combinatorial miR‑143/506 treatment downregulated CDK4 and CDK1 levels, and induced apoptosis in LC cells, while sparing normal lung fibroblasts. Moreover, the combinatorial miR treatment demonstrated a comparable activity to clinically tested cell cycle inhibitors in inhibiting cell cycle progression, by presenting substantial inhibition at the G1/S and G2/M cell cycle transitions. More importantly, the miR‑143/506 treatment presented a broader application, effectively downregulating CDK1 and CDK4 levels, and reducing cell growth in PC cells. These findings suggest that the miR‑143/506 combination acts as a promising approach to inhibit cell cycle progression for cancer treatment with minimal toxicity to normal cells.
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April-2021
Volume 45 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Hossian AN, Mackenzie GG and Mattheolabakis G: Combination of miR‑143 and miR‑506 reduces lung and pancreatic cancer cell growth through the downregulation of cyclin‑dependent kinases. Oncol Rep 45: 2, 2021
APA
Hossian, A.N., Mackenzie, G.G., & Mattheolabakis, G. (2021). Combination of miR‑143 and miR‑506 reduces lung and pancreatic cancer cell growth through the downregulation of cyclin‑dependent kinases. Oncology Reports, 45, 2. https://doi.org/10.3892/or.2021.7953
MLA
Hossian, A. N., Mackenzie, G. G., Mattheolabakis, G."Combination of miR‑143 and miR‑506 reduces lung and pancreatic cancer cell growth through the downregulation of cyclin‑dependent kinases". Oncology Reports 45.4 (2021): 2.
Chicago
Hossian, A. N., Mackenzie, G. G., Mattheolabakis, G."Combination of miR‑143 and miR‑506 reduces lung and pancreatic cancer cell growth through the downregulation of cyclin‑dependent kinases". Oncology Reports 45, no. 4 (2021): 2. https://doi.org/10.3892/or.2021.7953