MicroRNA therapy could be a powerful tool to correct the CSC dysregulation?

Medical Hypothesis: No small matter: microRNAs - key regulators of cancer stem cells by Qing Ji, David Karnak, Ping Hao, Rongquan Wang and Liang Xu, Int J Clin Exp Med 2010(Mar 12); 3(1): 84-7 [FriendFeed entry][Connotea bookmark][Full text via PMC]. PubMed Abstract:

Emerging evidence demonstrates that both tumor suppressor and oncogenic miRNAs play an essential role in stem cell self-renewal and differentiation by negatively regulating the expression of certain key genes in stem cells. It seems logical that they may also be critical players in cancer stem cells. Though small in size, miRNAs play a key role in the epigenetic regulation of cancer stem cells. Specifically, the imbalance of oncogenic vs. tumor suppressor miRNAs may lead to dysregulation of cancer stem cells, thus causing excessive self-renewal and survival of cancer stem cells, and resistance to chemo/radiotherapy. We postulate that restoring the balance of miRNAs will correct this dysregulation via the direct and simultaneous modulation of downstream stem cell pathways involved in cancer stem cell self-renewal and/or differentiation. The resultant restoration of key regulatory pathways could improve therapeutic response. Restoring tumor suppressor miRNAs and/or inhibiting oncogenic miRNAs may provide a novel molecular therapy for human cancers, potentially via modulating cancer stem cells.

Molecular link connecting breast cancer SCs with normal SCs

Stanford scientists find common trigger in cancer and normal stem cell reproduction, EurekAlert, August 6, 2009. First paragraph:

Researchers at Stanford University School of Medicine have discovered, for the first time, a common molecular pathway that is used by both normal stem cells and cancer stem cells when they reproduce themselves.

See also: Common Trigger In Cancer And Normal Stem Cell Reproduction Found, ScienceDaily, August 7, 2009. About the article:

Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells by Yohei Shimono and 14 co-authors, including Michael F Clarke, Cell 2009(Aug 7); 138(3): 592-603. [FriendFeed entry][PubMed Citation]. Summary:

Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We found 37 microRNAs that were differentially expressed between human BCSCs and nontumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429, and miR-183-96-182 were downregulated in human BCSCs, normal human and murine mammary stem/progenitor cells, and embryonal carcinoma cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. miR-200c inhibited the clonal expansion of breast cancer cells and suppressed the growth of embryonal carcinoma cells invitro. Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs invivo. The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells.

For a commentary, see the latter part of: Breast cancer stem cells resemble healthy stem cells, resist chemotherapy by Monya Baker, The Niche, August 10, 2009.

MicroRNA-181 and liver cancer

Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells by Junfang Ji and 15 co-authors, including Carlo M Croce and Xin Wei Wang, Hepatology 2009(Aug); 50(2): 472-80. [PubMed Abstract][Full text of author manuscript, available in PMC 2009(Aug 5)].

See also: EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features by Taro Yamashita and 15 co-authors, including Xin Wei Wang, Gastroenterology 2009(Mar); 136(3): 1012-24.e4 [Epub 2008(Dec 5)]. [PubMed Abstract].

And: New kids on the block: Diagnostic and prognostic microRNAs in hepatocellular carcinoma by Junfang Ji and Xin Wei Wang, Cancer Biology & Therapy 2009(Sep 15); 8(18) [Forthcoming].

News release about microRNAs

UCSF team moves in on mechanism in stem cell growth, possibly cancer, News Release, UCSF News Office, November 13, 2008. Excerpt:

In recent years, microRNAs have been implicated in cancer stem cells, cancer metastases, and even in psychological and metabolic diseases.

The news release is about this publication: Embryonic stem cell–specific microRNAs regulate the G1-S transition and promote rapid proliferation by Yangming Wang and 5 co-authors, including Robert Blelloch, Nat Genet 2008(Nov 2) [Epub ahead of print]. [PubMed Citation]. The article isn't freely accessible.