Long noncoding RNA RHPN1-AS1 exerts pro-oncogenic actions in osteosarcoma by functioning as a molecular sponge of miR-506 to positively regulate SNAI2 expression
Authors: Limin Wang
Yanbing Liu
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RHPN1 antisense RNA 1; microRNA-506; snail family zinc finger 2.
Affiliations: Department of Spinal Surgery, Shijiazhuang Third Hospital, Shijiazhuang, Hebei, P.R. China

Abstract:  The long noncoding RNA, RHPN1 antisense RNA 1 (RHPN1-AS1), performs important regulatory actions in the progression of many human cancers. In this study, we aimed to analyze RHPN1-AS1 expression in osteosarcoma (OS) and to assess the influence of RHPN1-AS1 knockdown on the malignant behavior of OS cells. The molecular mechanisms by which RHPN1-AS1 affects the oncogenicity of OS were explored too. The expression of RHPN1-AS1 in OS was measured by RT-qPCR. The effects of the RHPN1-AS1 silencing in OS cells were studied both in vitro (in a Cell Counting Kit-8 assay, apoptosis analysis, and Transwell migration and invasion assays) and in vivo (by means of tumor xenografts in nude mice). Herein, RHPN1-AS1 expression was found to be significantly upregulated in OS tissues and cell lines. The elevated expression of RHPN1-AS1 closely correlated with the tumor size, TNM stage, distal metastasis and shorter overall survival in patients with OS. The depletion of RHPN1-AS1 restrained OS cell proliferation, migration, and invasion, and exerted proapoptotic effects in vitro. Furthermore, the knockdown of RHPN1-AS1 effectively reduced the tumor growth of OS cells in vivo. As for the mechanism, RHPN1-AS1 increased snail family zinc finger 2 (SNAI2 also known as SNAIL2) expression by acting as a competing endogenous RNA of miR-506. Notably, increasing the amount of miR-506 partially reversed the effects of the RHPN1-AS1 downregulation on OS cells. In conclusion, RHPN1-AS1 contributes to the malignancy of OS cells in vitro and in vivo, largely via upregulation of the miR-506-SNAI2 axis output. 

Retracted: No

PubPeer comments:
 Fig 6c. Representative images of tumor xenografts collected from groups u201csh-RHPN1-AS1u201d and u201cshNC.u201d ![file] This is one of a series of xenograft line-ups that were evidently photographed in the same laboratory, despite appearing in papers from unrelated teams of authors from different institutions. All use the same ruler to provide scale, with a distinctive scratch near the 2 . Here for instance, - Fig 7B from [Li et al (2020)] .  Representative images of tumor xenografts collected from short hairpin RNA (sh)-LINC00525 and control (sh-NC) groups . - Fig 6A from [Dai et al (2020)] .  After 28 days post-inoculation, mice were euthanized and tumor xenografts were dissected and photographed . ![file] Other examples in the linked threads. Note the addition of a second scratch over the 8 in some appearances of the ruler; it was evidently treated roughly. , 
 - *[left]* Fig 5d. - *[right]* Fig 6E from  Long noncoding RNA TTN-AS1 enhances the malignant characteristics of osteosarcoma by acting as a competing endogenous RNA on microRNA-376a thereby upregulating dickkopf-1 ([Li et al 2019] ). ![file] , 
 - *[left]* Fig 5K. - *[right]* Fig 6D from  Long Noncoding RNA FGD5-AS1 Acts as a Competing Endogenous RNA on microRNA-383 to Enhance the Malignant Characteristics of Esophageal Squamous Cell Carcinoma by Increasing SP1 Expression ([Gao et al 2020] ) **[retracted]**. ![file] ----------------------- - *[left]* Fig 5j. - *right]* Fig 4F from  Long Noncoding RNA DLGAP1-AS1 Promotes the Aggressive Behavior of Gastric Cancer by Acting as a ceRNA for microRNA-628-5p and Raising Astrocyte Elevated Gene 1 Expression ([Deng et al 2020] ) **[retracted]**. ![file] ,