LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis

Abstract

Aim: To explore the mechanism by which long non-coding RNA (lncRNA) TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the microRNA miR-134-5p/malignant brain tumour domain containing 1 (MBTD1) axis.Results: The lncRNA TTN-AS1 was highly expressed in osteosarcoma and was associated with poor prognosis. The lncRNA TTN-AS1 promoted cell viability and inhibited apoptosis. MiR-134-5p targeted MBTD1, which was regulated by lncRNA TTN-AS1. MBTD1 was highly expressed in osteosarcoma and was associated with poor prognosis. MBTD1 promoted cell viability and inhibited apoptosis, and knockdown of MBTD1 reversed the cancer-promoting effects of lncRNA TTN-AS1. Downregulation of lncRNA TTN-AS1 reduced drug resistance.Conclusion: In osteosarcoma, lncRNA TTN-AS1 promoted the expression of MBTD1 by targeting miR-134-5p and regulated cell growth, apoptosis and drug resistance.Methods: The expression characteristics of genes in osteosarcoma patients were analysed using bioinformatics. Plasmid transfection technology was applied to silence or overexpress lncRNA TTN-AS1, miR-134-5p and MBTD1. Western blotting and quantitative polymerase chain reaction (qPCR) were used to detect protein and RNA, respectively. A cell counting kit 8 (CCK-8) and flow cytometry were used to detect cell viability and apoptosis. The effects of lncRNA TTN-AS1 and MBTD1 on osteosarcoma in vivo were studied by using a tumour burden assay.

LncRNA TTN‐AS1/miR‐134‐5p/PAK3 axis regulates the radiosensitivity of human large intestine cancer cells through the P21 pathway and AKT/GSK‐3β/β‐catenin pathway

“…As radiotherapy is a very important treatment for esophageal cancer patients, radiotherapy resistance has been attracting more and more attention from clinicians and researchers in the field. Previous studies have found that radiotherapy can induce tumor cell apoptosis and that tumor sensitivity to radiotherapy is consistent with tumor cell sensitivity to apoptosis (Simpson & Scholefield, 2008;Tut et al, 2015 (Fu et al, 2019), we found here a potential similar molecular mechanism for TTN-AS1 to inhibit apoptosis. Recently, miR-134 has been identified as a potential cancer suppressor and identified as deregulated in various types of human cancer, such as lung cancer, glioblastoma, breast cancer, colorectal cancer, and others (Pan et al, 2017).…”

“…***p < .001 versus control group, ### p < .001 versus miR-134-5p-NC group. p Value is calculated by one-way ANOVA followed by Duncan's test (Fu et al, 2019). Moreover, our results provide clear evidence that TTN-AS1 increases X-ray resistance of human large intestine cancer cells in vitro.…”

The clinical prognostic value of lncRNA FAM83H-AS1 in cancer patients: a meta-analysis

“…Increasing evidence has indicated that lncR-NAs play an important role in various human diseases, especially in malignant tumors [21][22][23][24]. Antisense long non-coding RNAs, such as TTN-AS1, IDH1-AS1 and AFAP-AS1, have been reported in tumors and closely related to the prognosis, development, invasion and metastasis of tumors [25][26][27].…”

The predictive value of lncRNA MIR31HG expression on clinical outcomes in patients with solid malignant tumors

“…Accumulating evidences have showed that aberrant expression of lncRNA could drive tumor phenotypes, including initiation, invasion, and metastasis, via interacting with other cellular macromolecules [9]. More recently, emerging lncRNAs have been identified and characterized as crucial factors in tumorigenesis, with certain reports highlighting them as biomarkers and targets in various cancers, such as breast cancer antiestrogen resistance 4 (BCAR4) [10], small nucleolar RNA host gene 16 (SNHG16) [11], and TTN antisense RNA 1 (TTN-AS1) [12].…”