MicroRNA regulation of K-Ras in pancreatic cancer and opportunities for therapeutic intervention

Saswati Karmakar, Garima Kaushik, Ramakrishna Nimmakayala, Satyanarayana Rachagani, Moorthy Palanimuthu Ponnusamy, Surinder Kumar Batra

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

The Ras family of GTPases is involved in cell proliferation, cell survival, and angiogenesis. It is upregulated in several cancers, including pancreatic cancer (PC) and leads to uncontrolled growth and aggressiveness. PC is well known to be a lethal disease with poor prognosis, plagued by limited therapeutic modalities. MicroRNAs (miRNAs), which are short non-coding RNA molecules, have recently emerged as regulators of signaling networks and have shown potential to target pathway components for therapeutic use in several malignancies. K-Ras mutations are widespread in PC cases (90%), with mutations detectable as early as pancreatic intraepithelial neoplasias and in later metastatic stages alike; therefore, these mutations in K-Ras are obvious drivers and potential targets for PC therapy. Several K-Ras targeting miRNAs have lately been discovered, and many of them have shown promise in combating pancreatic tumor growth in vitro and in mouse models. However, the field of miRNA therapy is still in its infancy, and miRNA mimics or anti-miRNA oligonucleotides that target Ras pathway have thus far not been evaluated in PC patients. In this review, we summarize the role of several miRNAs that regulate oncogenic K-Ras signaling in PC, with their prospective roles as therapeutic agents for targeting K-Ras pathway.

Original languageEnglish (US)
Pages (from-to)63-71
Number of pages9
JournalSeminars in Cancer Biology
Volume54
DOIs
StatePublished - Feb 2019

Fingerprint

MicroRNAs
Pancreatic Neoplasms
Mutation
Neoplasms
Therapeutics
ras Proteins
Untranslated RNA
Therapeutic Uses
Growth
Oligonucleotides
Cell Survival
Cell Proliferation

Keywords

  • Anti-miRNA oligonucleotides (AMOs)
  • EGFR
  • Integrin
  • K-Ras
  • Let-7
  • MicroRNA
  • NF-kB
  • Pancreatic Cancer
  • RTK signaling
  • Ras mutations
  • Therapeutics
  • miR-126
  • miR-143/145
  • miR-193b
  • miR-206
  • miR-21
  • miR-217/216
  • miR-2923
  • miR-96
  • p53

ASJC Scopus subject areas

  • Cancer Research

Cite this

MicroRNA regulation of K-Ras in pancreatic cancer and opportunities for therapeutic intervention. / Karmakar, Saswati; Kaushik, Garima; Nimmakayala, Ramakrishna; Rachagani, Satyanarayana; Palanimuthu Ponnusamy, Moorthy; Batra, Surinder Kumar.

In: Seminars in Cancer Biology, Vol. 54, 02.2019, p. 63-71.

Research output: Contribution to journalReview article

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abstract = "The Ras family of GTPases is involved in cell proliferation, cell survival, and angiogenesis. It is upregulated in several cancers, including pancreatic cancer (PC) and leads to uncontrolled growth and aggressiveness. PC is well known to be a lethal disease with poor prognosis, plagued by limited therapeutic modalities. MicroRNAs (miRNAs), which are short non-coding RNA molecules, have recently emerged as regulators of signaling networks and have shown potential to target pathway components for therapeutic use in several malignancies. K-Ras mutations are widespread in PC cases (90{\%}), with mutations detectable as early as pancreatic intraepithelial neoplasias and in later metastatic stages alike; therefore, these mutations in K-Ras are obvious drivers and potential targets for PC therapy. Several K-Ras targeting miRNAs have lately been discovered, and many of them have shown promise in combating pancreatic tumor growth in vitro and in mouse models. However, the field of miRNA therapy is still in its infancy, and miRNA mimics or anti-miRNA oligonucleotides that target Ras pathway have thus far not been evaluated in PC patients. In this review, we summarize the role of several miRNAs that regulate oncogenic K-Ras signaling in PC, with their prospective roles as therapeutic agents for targeting K-Ras pathway.",
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