title: MiR-148a, a microRNA upregulated in the WNT subgroup tumors, inhibits invasion and tumorigenic potential of medulloblastoma cells by targeting Neuropilin 1.
abstract: Medulloblastoma, a common pediatric malignant brain tumor consists of four molecular subgroups viz. WNT, SHH, Group 3 and Group 4. MiR-148a is over-expressed in the WNT subgroup tumors, which have the lowest incidence of metastasis and excellent survival among all medulloblastomas. MiR-148a was expressed either in a transient manner using a synthetic mimic or in a stable doxycycline inducible manner using a lentiviral vector in non-WNT medulloblastoma cell lines. Expression of miR-148a to levels comparable to that in the WNT subgroup tumors was found to inhibit proliferation, clonogenic potential, invasion potential and tumorigenicity of medulloblastoma cells. MiR-148a expression in medulloblastoma cells brought about reduction in the expression of NRP1, a novel miR-148a target. Restoration of NRP1 expression in medulloblastoma cells was found to rescue the reduction in the invasion potential and tumorigenicity brought about by miR-148a expression. NRP1 is known to play role in multiple signaling pathways that promote tumor growth, invasion and metastasis. NRP1 expression in medulloblastomas was found to be associated with poor survival, with little or no expression in majority of the WNT tumors. The tumor suppressive effect of miR-148a expression accompanied by the down-regulation of NRP1 makes miR-148a an attractive therapeutic agent for the treatment of medulloblastomas.
authors.affiliation: Shirsat Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Kedar
authors.initials: K
authors.lastname: Yogi
authors.affiliation: Department of Pathology, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Epari
authors.initials: E
authors.lastname: Sridhar
authors.affiliation: Department of Pathology, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai, India.
authors.forename: Naina
authors.initials: N
authors.lastname: Goel
authors.affiliation: Department of Radiation Oncology, Tata Memorial Hospital, Tata Memorial Centre, Parel, Mumbai, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Jalali
authors.affiliation: Department of Neurosurgery, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Goel
authors.affiliation: Department of Surgical Oncology, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Aliasgar
authors.initials: A
authors.lastname: Moiyadi
authors.affiliation: Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Thorat
authors.affiliation: Shirsat Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Panwalkar
authors.affiliation: Shirsat Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Khire
authors.affiliation: Department of Radiation Oncology, Tata Memorial Hospital, Tata Memorial Centre, Parel, Mumbai, India.
authors.forename: Archya
authors.initials: A
authors.lastname: Dasgupta
authors.affiliation: Department of Surgical Oncology, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Shetty
authors.affiliation: Shirsat Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.
authors.forename: Neelam Vishwanath
authors.initials: NV
authors.lastname: Shirsat
keywords: Medulloblastoma; Neuropilin 1; WNT subgroup; invasion; miR-148a