Reovirus-associated reduction of microRNA-let-7d is related to the increased apoptotic death of cancer cells in clinical samples

被引：43

作者：

Nuovo, Gerard J. ^{[1
]}

Garofalo, Michela ^{[1
]}

Valeri, Nicola ^{[1
]}

Roulstone, Vicki ^{[2
]}

Volinia, Stefano ^{[1
]}

Cohn, David E. ^{[3
]}

Phelps, Mitch ^{[4
]}

Harrington, Kevin J. ^{[2
]}

Vile, Richard ^{[5
]}

Melcher, Alan ^{[2
]}

Galanis, Evanthia ^{[5
]}

Sehl, Sarah ^{[6
]}

Adair, Rob ^{[2
]}

Scott, Karen ^{[2
]}

Rose, Ailsa ^{[2
]}

Toogood, Giles ^{[2
]}

Coffey, Matthew C. ^{[6
]}

机构：

[1] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA

[2] Univ Leeds, Leeds Inst Mol Med, Leeds, W Yorkshire, England

[3] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Div Gynecol Oncol, Columbus, OH 43210 USA

[4] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA

[5] Mayo Clin, Dept Mol Med, Rochester, NY USA

[6] Oncolyt Biotech, Calgary, AB, Canada

来源：

MODERN PATHOLOGY | 2012年 / 25卷 / 10期

关键词：

apoptosis; caspase-3; microRNA-let-7d; PKR; Ras; reovirus; POLYMERASE-CHAIN-REACTION; ONCOLYTIC REOVIRUS; SIGNALING PATHWAY; COLON-CANCER; RAS; THERAPY; MODEL;

D O I：

10.1038/modpathol.2012.95

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

We analyzed the in situ molecular correlates of infection from cancer patients treated with reovirus. Melanoma, colorectal, and ovarian cancer samples from such patients showed variable infection of the cancer cells but not the intermingled benign cells. RT in situ PCR showed most cancer cells contained the viral genome with threefold less having productive viral infection as documented by either tubulin or reoviral protein coexpression. Productive infection in the cancer cells was strongly correlated with co-expression of p38 and caspase-3 as well as apoptosis-related death (P<0.001). The cancer cell apoptotic death was due to a marked viral-induced inhibition of microRNA-let-7d that, in turn, upregulated caspase-3 activity. In summary, reovirus shows a striking tropism to cancer cells in clinical samples. A rate-limiting factor of reovirus-induced cancer cell death is productive viral infection that operates via the marked reduction of microRNA-let-7d and concomitant elevated caspase-3 expression. Modern Pathology (2012) 25, 1333-1344; doi: 10.1038/modpathol.2012.95; published online 15 June 2012

引用

页码：1333 / 1344

页数：12

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