TY - JOUR
TI - PAPOLA contributes to cyclin D1 mRNA alternative polyadenylation and
promotes breast cancer cell proliferation
AU - Komini, Chrysoula
AU - Theohari, Irini
AU - Lambrianidou, Andromachi and
AU - Nakopoulou, Lydia
AU - Trangas, Theoni
JO - Journal of Cell Science
PY - 2021
VL - 134
TODO - 7
SP - null
PB - Company of Biologists Ltd
SN - 0021-9533, 1477-9137
TODO - 10.1242/jcs.252304
TODO - Poly(A) polymerase alpha; Cyclin D1; Alternative polyadenylation;
Poly(A) tail; Breast cancer
TODO - Poly(A) polymerases add the poly(A) tail at the 3 ` end of nearly all
eukaryotic mRNA, and are associated with proliferation and cancer. To
elucidate the role of the most-studied mammalian poly(A) polymerase,
poly(A) polymerase alpha (PAPOLA), in cancer, we assessed its expression
in 221 breast cancer samples and found it to correlate strongly with the
aggressive triple-negative subtype. Silencing PAPOLA in MCF-7 and
MDA-MB-231 breast cancer cells reduced proliferation and
anchorage-independent growth by decreasing steady-state cyclin D1
(CCND1) mRNA and protein levels. Whereas the length of the CCND1 mRNA
poly(A) tail was not affected, its 3 ` untranslated region (3 ` UTR)
lengthened. Overexpressing PAPOLA caused CCND1 mRNA 3 ` UTR shortening
with a concomitant increase in the amount of corresponding transcript
and protein, resulting in growth arrest in MCF-7 cells and DNA damage in
HEK-293 cells. Such overexpression of PAPOLA promoted proliferation in
the p53 mutant MDA-MB-231 cells. Our data suggest that PAPOLA is a
possible candidate target for the control of tumor growth that is mostly
relevant to triple-negative tumors, a group characterized by PAPOLA
overexpression and lack of alternative targeted therapies.
ER -