HOTAIR (homeobox transcript antisense RNA), one of the prototypical long non-coding RNAs, has been verified overexpressed in multiple carcinomas and has emerged as a promising novel anticancer target. Its well-established role is acting as a predictor of poor prognosis and promoting cancer cell metastasis. Recently, another important mission of HOTAIR was uncovered that targeting HOTAIR caused cancer cell apoptosis. Nevertheless, so far there is no published data elaborating the mechanism. Here, we report that microRNA miR-125a-5p decreases and releases caspase 2 to promote cancer cell apoptosis after HOTAIR knockdown. We applied siRNAs targeting HOTAIR to various cancer cells, and observed apoptosis in all of these cell lines. RNA sequencing detected that miR-125a-5p was decreased after HOTAIR knockdown and miR-125a-5p mimics could rescue the apoptosis induced by HOTAIR deficiency. Luciferase assays identified caspase 2, an initiator caspase, to be a new target of miR-125a-5p. Elevated expression and subsequent cleavage of caspase 2 was observed after HOTAIR knockdown or inhibition of miR-125a-5p. RNAi of caspase 2 could attenuate the apoptosis induced by HOTAIR knockdown. In 80 clinical colon cancer tissues, HOTAIR and miR-125a-5p levels were higher than adjacent tissues, whereas caspase 2 was lower. MiR-125a-5p expression level was significantly correlated with colon tumor size, lymph node metastasis and clinical stage. These findings indicate that miR-125a-5p decreases after HOTAIR knockdown to promote cancer cell apoptosis by releasing caspase 2. Our work reveals a previously unidentified apoptotic mechanism, which might be exploitable in anticancer drug development.

The properties of the nonlinear frequency shift (NFS) especially the fluid NFS from the harmonic generation of the ion-acoustic wave (IAW) in multi-ion species plasmas have been researched by Vlasov simulation. The pictures of the nonlinear frequency shift from harmonic generation and particles trapping are shown to explain the mechanism of NFS qualitatively. The theoretical model of the fluid NFS from harmonic generation in multi-ion species plasmas is given and the results of Vlasov simulation are consistent to the theoretical result of multi-ion species plasmas. When the wave number kλDe is small, such as kλDe = 0.1, the fluid NFS dominates in the total NFS and will reach as large as nearly 15% when the wave amplitude |eφ/Te| ∼ 0.1, which indicates that in the condition of small kλDe, the fluid NFS dominates in the saturation of stimulated Brillouin scattering especially when the nonlinear IAW amplitude is large.

The auto-resonant behavior of ion acoustic waves (IAWs) driven by stimulated Brillouin backscattering in supersonic flowing plasmas is self-consistently investigated by Vlasov simulations. Vlasov simulations show that the peak amplitude of the auto-resonant growing IAWs in the positive flow gradient is much larger than that in the negative flow gradient, which is contrary to the previous analysis (Wang et al 2018 Plasma Phys. Control. Fusion 60 025016). It is found that the IAW phase velocity remains unchanged in supersonic flowing plasmas, which significantly influences wave-particle interaction by changing the Landau damping and the coefficient of the kinetic nonlinear frequency shift in different position. As a result, the Landau damping of IAWs in the peak region in the negative case is stronger than that in the positive case, which has never been considered before. After considering its effects on particle trapping and, particularly, Landau damping of IAWs, theoretical predictions from three-wave mode equations are consistent with results by Vlasov simulations.

The effect of the kinetic nonlinear frequency shift (KNFS) on backward stimulated Brillouin scattering (SBS) in homogeneous plasmas and inhomogeneous flowing plasmas is investigated by three-wave coupled-mode equations. When the positive contribution to the KNFS from electrons as well as the negative contribution from ions is included, the net KNFS can become positive at a large electron-ion temperature ratio ZT T e i . In homogeneous plasmas, KNFS can greatly reduce the SBS reflectivity at low or large ZT T e i but has a weak effect on SBS at ZT T e iwhere the positive frequency shifts from electrons almost cancels out the negative shifts from ions. In inhomogeneous plasmas, the net negative frequency shift can enhance the backward SBS reflectivity for the negative gradient of the plasma flowing, and can suppress the reflectivity for the positive case. On the contrary, the net positive frequency can suppress the reflectivity for the negative case of the flowing gradient and enhance the reflectivity for the positive case. This indicates that the SBS in inhomogeneous flowing plasmas can be controlled by changing the sign of the nonlinear frequency shift.

The anti-Stokes scattering and Stokes scattering in stimulated Brillouin scattering (SBS) cascade have been researched by the Vlasov-Maxwell simulation. In the high-intensity laser-plasmas interaction, the stimulated anti-Stokes Brillouin scattering (SABS) will occur after the second stage SBS rescattering. The mechanism of SABS has been put forward to explain this phenomenon. And the SABS will compete with the SBS rescattering to determine the total SBS reflectivity. Thus, the SBS rescattering including the SABS is an important saturation mechanism of SBS, and should be taken into account in the high-intensity laser-plasmas interaction.PACS numbers: 52.38. Bv, 52.35.Fp, 52.35.Mw, 52.35.Sb Backward stimulated Brillouin scattering (SBS), i.e., the Stokes scattering, is a three-wave interaction process where an incident electromagnetic wave (EMW) decays into a backscattered EMW and a forward propagating ion-acoustic wave (IAW). Backward SBS leads to a great energy loss of the incident laser and is detrimental in inertial confinement fusion (ICF) [1][2][3]. Therefore, SBS plays an important role in the successful ignition goal of ICF. Many mechanisms for the saturation of SBS have been put forward, including the creation of cavitons in plasmas [4][5][6][7], frequency detuning due to particles trapping [8][9][10][11], coupling with higher harmonics [12,13], increasing linear Landau damping by kinetic ion heating [14,15], and so on. However, if the pump light intensity is large enough, or the IAW Landau damping is low enough, it is possible for the scattered light to be scattered again. The multi-stage rescattering of SBS is called SBS cascade [16][17][18]. In this paper, the rescattering of SBS is observed and found to be an important saturation mechanism of SBS in high-intensity laser region. Although the theoretical work on SBS rescattering [16] gives a prediction of reduced SBS reflectivity under the assumption that the incident light is allowed to scatter only twice. In fact, the multiple SBS rescattering will occur in high-intensity laser region [17,18], and different stage SBS rescatterings will have the different effects on the total reflectivity or the total transmitivity of SBS. This paper will give a detail analysis of each stage SBS rescattering evolution with time, and demonstrate the SBS rescatterings compete with each other to affect the reflectivity or the transmitivity.In addition to the Stokes scattering in the SBS cascade, which is a common scattering mechanism of SBS, there exists a novel scattered light of a higher frequency than the pump light frequency. This novel scattering is called stimulated anti-Stokes Brillouin scattering (SABS). The SABS is that a pump EMW couples with an IAW to produce a backward scattered EMW, the three waves satisfy the frequency and wave vector match conditions. The anti-Stokes Raman scattering was researched in the intense light interaction with gas [19,20], liquid [21] and solid [22]. And the anti-Stokes scattering of SBS was researched in the intense light inte...