Knockdown of lncRNA AL928768.3 inhibits multiple myeloma cell proliferation by inducing cell cycle arrest in G0/G1 phase

Background: Multiple myeloma (MM) is a B-lymphocyte-derived malignancy. It ranks as the second most common hematological malignancy, with relatively high morbidity and mortality. However, the molecular mechanisms of MM occurrence and development remain elusive. This study found that long non-coding RNA AL928768.3 (lncRNA AL) was abnormally expressed in MM samples. However, the effect and molecular mechanism of lncRNA AL on the occurrence and development of MM remains unclear.

Methods: Bone marrow fluids of MM patients (n=54) and volunteers (n=13) were collected and CD138⁺ cells were isolated. The expression level of lncRNA AL in MM cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the correlation between the expression level of lncRNA AL and the clinicopathological features of patients was analyzed. Lentiviral vectors targeting lncRNA AL knockdown were constructed and transfected into cells. After transfection, the effects of lncRNA AL knockdown on MM cell proliferation and the cell cycle were detected by the CCK-8 assay, clone formation assay, and flow cytometry. The effect of lncRNA AL knockdown on MM cell cycle-related proteins was detected by Western blot. In addition, tumorigenicity experiments were performed in nude mice to detect the effect of lncRNA AL knockdown on MM cell proliferation in vivo.

Results: LncRNA AL was highly expressed in MM patient samples and cell lines, and was significantly correlated with the disease stage of patients. Knockdown of lncRNA AL significantly inhibited the proliferation and colony formation of MM cells and induced cell cycle arrest in G0/G1 phase. Western blot analysis showed that knockdown of lncRNA AL significantly inhibited the expression of CDK2 and cyclin D1 and promoted the expression of cyclin suppressor p21. Knockdown of lncRNA AL significantly inhibited the proliferation of MM cells in nude mice.

Conclusions: LncRNA AL was highly expressed in MM patients. Knockdown of this gene significantly inhibited the proliferative ability of MM cells and induced cell cycle arrest in G0/G1 phase. Therefore, lncRNA AL may be a novel biological target molecule for the early diagnosis, treatment, and prognostic evaluation of MM patients.