The Effect Of MALAT-1 On The Growth Of Osteosarcoma And The Relationship Between MALAT-1 And Clinical Features

Malignant neoplasms have become an important factor that threat people’s health nowadays.Osteosarcoma,which is more likely to happen in adolescent,brings a heavy psychological pressure and economic burden to the community and the patients’ families because of its highly malignancy,early distant metastasis,high morbidity and high mortality.With the continuous development of chemotherapy strategy and artificial joint material technology,the treatment strategy of osteosarcoma has achieved rapid development and the limb salvage rate and 5-year survival rate of patients has improved.However,the current therapeutic efficacy is still limited.The survival rate is still low for osteosarcoma patients with resistance to chemotherapeutic drugs,recurrence or metastasis.The treatment of osteosarcoma has encountered a “bottleneck” in the last 5 to 10 years.The molecular targeted therapy may be a new breakthrough in the treatment of osteosarcoma.At present,the role of long non-coding RNA(lnc RNA)in neoplasms is being explored.Many researchers found that many lncRNAs are expressed abnormally in different tumors,and the expression of these lncRNAs was closely related to the tumor staging and patients’ prognosis.Many neoplasms’ characteristics,such as invasion,migration and metastasis,can be changed when the expression of some lncRNAs are regulated.These findings suggest that lncRNAs may be the new targets for neoplasms.The MALAT-1,which is short for metastasis-associated lung adenocarcinoma transcript 1,is one of the earliest lncRNAs found in human diseases.MALAT-1 has been confirmed to play an important role in the proliferation,invasion and metastasis of various neoplasms.However,the studies on the expression of MALAT-1 in osteosarcoma are still few and have some limitations.Therefore,we conducted this study aiming to further explore the expression and role of MALAT-1 in osteosarcoma so that we may find new indicators for the evaluation of osteosarcoma and provide evidence and reference for the possible gene therapy and molecular targeted therapy in the future.On one hand,we observed the influence of MALAT-1 expression level on the growth of osteosarcoma by planting tumors on the nude mice.On the other hand,we took advantages of the discipline superiority of bone neoplasms in the collection of osteosarcoma tissues and adjacent normal tissues.By comparing the MALAT-1 expression in the osteosarcoma tissues andadjacent normal tissues in patients,and analyzing the patients’ clinical dates,we could explore the relationship between clinical features and MALAT-1 expression in osteosarcoma.Part I: The effect of MALAT-1 expression on the growth of osteosarcoma in nude mice.In this part,we cultured the osteosarcoma H2 OS cell lines in which MALAT-1 was down-regulated stably with the technique of lentivirus transfection.Twelve nude mice were divided into experimental group and control group.The nude mice in the experimental group were subcutaneously implanted by the osteosarcoma H2 OS cell lines in which MALAT-1 was down-regulated stably.The nude mice in the control group were subcutaneously implanted by the osteosarcoma H2 OS cell lines transfected by no-load lentivirus in which the expression of MALAT-1 was normal.The growth of subcutaneous tumor in nude mice was observed,and the differences of the tumor volume,tumor weight,HE staining and immunohistochemistry were compared between the two groups.We confirmed that the tumor in experimental group grew slower and had smaller volume and weight in the same growth time when compared with the control group.HE staining and immunohistochemistry showed that there were increased matrix composition and decreased cell density and PCNA expression in the tumor of experimental group.This result suggested that down-regulated MALAT-1 expression can inhibit the growth of osteosarcoma,promote apoptosis of osteosarcoma cells,and reduce the invasion of osteosarcoma cells.There is no literature on the effect of MALAT-1 expression in osteosarcoma at the aspects of pathology currently.Part II: Study on the relationship between MALAT-1 expression and clinical features of osteosarcoma patients.In the second part of this study,we collected the osteosarcoma tissues and adjacent normal tissues from each patient.Then we measured the MALAT-1 expression in specimens and explore the relationship between the MALAT-1 expression and the clinical features including patients’ age,sex,tumor site,alkaline phosphatase,tumor staging,purpose of surgery(biopsy or radical operation),chemotherapy and so on.This is a detailed study on the relationship between MALAT-1 expression and clinical features of patients.The result showed that the expression of MALAT-1 is related to the osteosarcomapatients’ clinical stage and neoadjuvant chemotherapy.Compared to the patients whose clinical stage are IIA,the patients whose clinical stage are IIB are more likely to be seen that the expression of MALAT-1 in osteosarcoma tissues is higher than that in adjacent normal tissues.The expression of MALAT-1 in osteosarcoma tissues is more likely to be higher than that in adjacent normal tissues in patients who have received neoadjuvant chemotherapy.However,the expression of MALAT-1 in osteosarcoma tissues is more likely to be lower than that in adjacent normal tissues in patients who have not received neoadjuvant chemotherapy.This result shows that the expression of MALAT-1 may be specific in osteosarcoma compared with other neoplasms.Because of the special treatment and complex clinical features of osteosarcoma,it needs further study on the effect of MALAT-1 in the clinical assessment and molecular targeted therapy.