Altered Long Noncoding RNA Expression Profile in Multiple Myeloma Patients with Bisphosphonate-Induced Osteonecrosis of the Jaw

Allegra, Alessandro; Mania, Manuela; D’Ascola, Angela; Oteri, Giacomo; Siniscalchi, Enrico Nastro; Avenoso, Angela; Innao, Vanessa; Scuruchi, Michele; Musolino, Caterina; Campo, Salvatore

doi:10.1155/2020/9879876

Cited by 19 publications

(18 citation statements)

References 70 publications

(71 reference statements)

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“…Similarly, our results elicited that si-MALAT1 transfection upregulated the expressions of these osteoclast-related genes in Mø. Knockdown of MALAT1 is probably associated with the elevated osteoclast generation related to bone lesions (Allegra et al, 2020). Taken together, downregulation of MALAT1 repressed osteogenic differentiation of BMSCs and facilitated osteoclastic differentiation of Mø.…”

Section: Discussionmentioning

confidence: 91%

LncRNA metastasis‐associated lung adenocarcinoma transcript‐1 promotes osteogenic differentiation of bone marrow stem cells and inhibits osteoclastic differentiation of Mø in osteoporosis via the miR‐124‐3p/IGF2BP1/Wnt/β‐catenin axis

2022

J Tissue Eng Regen Med

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Osteoporosis is defined as a skeletal disorder characterized by impairment in bone strength. The potential application of lncRNAs as therapeutic targets for osteoporosis has been unveiled. This study investigated the regulatory mechanism of lncRNA MALAT1 in the differentiation of bone marrow stem cells (BMSCs) and macrophages (Mø) in osteoporosis. MALAT1 expression in peripheral blood of elderly osteoporosis patients and healthy volunteers was detected. BMSCs and mononuclear Mø were isolated and cultured. Osteogenic differentiation of BMSCs and osteoclastic differentiation of Mø were induced. BMSCs and Mø were transfected with si-MALAT1, miR-124-3p mimics, miR-124-3p inhibitor, or pcDNA IGF2BP1, followed by detection of cell differentiation. The target microRNAs (miRs) and downstream genes and signaling pathways of MALAT1 were examined. The ovariectomy-induced mouse model of osteoporosis was established, and the mice were injected with pcDNA-MALAT1. MALAT1 was downregulated in osteoporosis patients, increased in BMSCs after osteogenic differentiation, and diminished in Mø after osteoclastic differentiation. Downregulation of MALAT1 repressed osteogenic differentiation of BMSCs and facilitated osteoclastic differentiation of Mø. MALAT1 upregulated IGF2BP1 expression by competitively binding to miR-124-3p. miR-124-3p silencing reversed the effect of si-MALAT1 on BMSCs and Mø differentiation, and IGF2BP1 upregulation averted the effect of overexpressed-miR-124-3p by activating the Wnt/ β-catenin pathway. Upregulation of MALAT1 activated the Wnt/β-catenin pathway and attenuated bone injury in mice. In conclusion, lncRNA MALAT1 promoted the osteogenic differentiation of BMSCs and inhibited osteoclastic differentiation of Mø in osteoporosis via the miR-124-3p/IGF2BP1/Wnt/β-catenin axis.

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Section: Discussionmentioning

confidence: 91%

LncRNA metastasis‐associated lung adenocarcinoma transcript‐1 promotes osteogenic differentiation of bone marrow stem cells and inhibits osteoclastic differentiation of Mø in osteoporosis via the miR‐124‐3p/IGF2BP1/Wnt/β‐catenin axis

2022

J Tissue Eng Regen Med

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“…None of the proposed treatment protocols have been demonstrated to have complete success, but only partial resolution of MRONJ cases [ 17 , 46 ]. There is a need to better understand the role that osteoimmunity plays [ 28 ] and whether or not a genetic predisposition exists among populations [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Oral Complications in Cancer Patients–Medication-Related Osteonecrosis of the Jaw (MRONJ)

Migliorati

2022

Front. Oral. Health

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Medication-Related Osteonecrosis of the Jaw (MRONJ) was first reported in 2003. Despite the progress in the understanding of this oral complication in cancer patients for the past 18 years, there is still discussion about the best way to define MRONJ, prevent the complication, how to diagnose, and the options of treatment available. The initial reports associated MRONJ to bisphosphonates and denosumab, medications that work as bone-modifying agents. Later, other agents such as the antiangiogenics, have also been reported to cause the oral complication, either alone or in combination with antiresorptives. Initially, these medications were prescribed to patients with osteoporosis and cancers patients with bone metastasis. Today, because of the effect of the medications in the bone remodeling system, patients with several other diseases such as giant cell tumors, rheumatoid arthritis, Paget's disease of bone, fibrous dysplasia, osteogenesis imperfecta, are managed with these medications, significantly increasing the population of individuals at risk for developing MRONJ. This mini review focused on the cancer patient. It updates the dental clinician on the recent scientific literature about MRONJ and provides information on how to diagnose and manage patients being treated with these medications, suggests protocols to prevent the development of MRONJ, and present ways to manage those patients who develop the oral complication.

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“…LncRNAs indicate a class of RNA transcripts larger than 200 nucleotides with no function of encoded proteins [ 133 , 134 ]. In the study of MM, lncRNAs were employed as competitive endogenous RNAs or a miRNA sponge.…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

Potential Role of microRNAs in inducing Drug Resistance in Patients with Multiple Myeloma

Allegra

Ettari

Innao

et al. 2021

Cells

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The prognosis for newly diagnosed subjects with multiple myeloma (MM) has significantly progressed in recent years. However, most MM patients relapse and after several salvage therapies, the onset of multidrug resistance provokes the occurrence of a refractory disease. A continuous and bidirectional exchange of information takes place between the cells of the microenvironment and neoplastic cells to solicit the demands of cancer cells. Among the molecules serving as messengers, there are microRNAs (miRNA), a family of small noncoding RNAs that regulate gene expression. Numerous miRNAs are associated with drug resistance, also in MM, and the modulation of their expression or activity might be explored to reverse it. In this review we report the most recent studies concerning the relationship between miRNAs and chemoresistance to the most frequently used drugs, such as proteasome inhibitors, steroids, alkylating agents and immunomodulators. The experimental use of antagomirs or miRNA mimics have successfully been proven to counteract chemoresistance and display synergistic effects with antimyeloma drugs which could represent a fundamental moment to overcome resistance in MM treatment.

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Altered Long Noncoding RNA Expression Profile in Multiple Myeloma Patients with Bisphosphonate-Induced Osteonecrosis of the Jaw

Cited by 19 publications

References 70 publications

LncRNA metastasis‐associated lung adenocarcinoma transcript‐1 promotes osteogenic differentiation of bone marrow stem cells and inhibits osteoclastic differentiation of Mø in osteoporosis via the miR‐124‐3p/IGF2BP1/Wnt/β‐catenin axis

LncRNA metastasis‐associated lung adenocarcinoma transcript‐1 promotes osteogenic differentiation of bone marrow stem cells and inhibits osteoclastic differentiation of Mø in osteoporosis via the miR‐124‐3p/IGF2BP1/Wnt/β‐catenin axis

Oral Complications in Cancer Patients–Medication-Related Osteonecrosis of the Jaw (MRONJ)

Potential Role of microRNAs in inducing Drug Resistance in Patients with Multiple Myeloma

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