Passage
Overexpression of the miR-17~92 gene cluster occurs in many human cancers involving c-Myc, a gene coding for a transcription factor that regulates expression of proteins such as p21, an inhibitor of cell cycle progression. miR-17~92 encodes six distinct microRNAs (miRNAs) that can be divided into four families based on sequence identity at positions 2-7 (Table 1) .Table 1 Sequence Identities of miRNA Families Encoded by the mir-17∼92 Gene Cluster
Experiment 1Two independent, diffuse B-cell lymphoma cell lines were used to study the functional relationship between miR-17~92 transcripts and c-Myc in cancer pathogenesis. The first cell line was derived from Eμ-Myc mice (Eμ) , which overexpress a c-Myc transgene under the control of a B-cell-specific enhancer that induces early development of B-cell lymphoma. The second cell line was derived from Eμ-Myc mice carrying a miR-17∼92 knockout allele (Δ/Δ) . As shown in Figure 1, researchers measured the growth of both cell lines, as well as that of Δ/Δ cells infected with a retrovirus expressing the entire miR-17∼92 cluster (Δ/Δ + miR-17∼92) .
Figure 1 Growth curves of Eμ cells, Δ/Δ cells, and Δ/Δ + miR-17∼92 cells (error bars = standard deviation) Experiment 2To assess the relative contribution of each miRNA to the oncogenic ability of the miR-17∼92 cluster, Δ/Δ cell lines were transduced with an empty vector or with miR-17∼92 mutant allele constructs that were engineered to lack expression of miRNA from at least one of the four families. In each of the constructs, the family that was knocked out of the vector is indicated by the Δ symbol. After verifying that the transduced cells correctly expressed the desired miRNA, the fraction of apoptotic cells in each line was measured (Figure 2) .
Figure 2 Percentage of apoptotic cells in Eμ cells and Δ/Δ cells transduced with the indicated miR-17~92 construct (error bars = standard deviation)
Adapted from Mu P, Han YC, Betel D, et al. Genetic dissection of the miR-17~92 cluster of microRNAs in Myc-induced B-cell lymphomas. Genes Dev. 2009;23(24) :2806-11.
-When expressed, the most likely function of the products generated by the miR-17~92 gene cluster is to:
A) assist with the primary enzymatic functions of the ribosome.
B) facilitate the processing of pre-mRNA in the cell nucleus.
C) interfere with gene expression by binding transcripts with complementary nucleotide sequences.
D) prevent small nuclear ribonucleoproteins from forming a large RNA-protein complex.
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